Baseline Serum Research Articles

Follicular Fluid Vanin-1 Levels in Patients Undergoing Ivf: A Preliminary Study

This preliminary study was designed to determine follicular fluid (FF) vanin-1 levels, to assess their relation to serum vanin-1 and to reveal their potential to predict the outcome of in vitro fertilization (IVF). Eighteen unselected, consecutive women undergoing IVF were included. Serum and pooled FF samples were obtained simultaneously during routine IVF procedures. Vanin-1 levels were measured by using commercially available ELISA kits. As most of the values were below 0.6 ng/mL, the data are given as optical density. It was found that vanin-1 can be detected in FF and that it is not significantly related to its maternal serum levels (p = 0.06). FF vanin-1 levels proved to be higher in non-pregnant as compared to pregnant women (p < 0.04). There are significant positive relationships between the FF to serum vanin-1 ratio and body mass index (BMI, p < 0.02), anti-Müllerian hormone (AMH, p < 0.02) and baseline serum estradiol (p < 0.01). Moreover, the FF/serum vanin-1 ratio tended to increase with cumulative FSH dose, but this increase did not reach statistical significance (p = 0.064). It may be concluded that FF vanin-1 may serve as a biomarker to predict IVF outcome. To confirm this contention, further studies are to be performed.

P0093 Identification of metabolic predictive biomarkers of response to Inflammatory Bowel Disease treatment

Abstract Background The therapeutic goal in inflammatory bowel disease (IBD), which includes Crohn´s disease (CD) and ulcerative colitis (UC), is the control of the inflammatory process frequently through biologic and JAK-inhibitor therapies, which are generally expensive and may induce adverse effects. Unfortunately, only one-third of patients respond to these treatments, and there are no markers that accurately predict this response. The aim of this study was to identify potential serum and urinary metabolic biomarkers predictive of IBD response to different drugs at baseline (before treatment), which could facilitate the selection of the most appropriate therapy for each patient. Methods A prospective multicenter study was conducted including CD and UC patients who initiated biologic (anti-TNF, ustekinumab or vedolizumab) or JAK-inhibitor (tofacitinib) therapies. Patients were assessed at 14 weeks to determine if they had achieved an endoscopic response, based on the SES-CD and on the endoscopic sub-score of the Partial Mayo Score. The analyses of the serum and urine metabolome, along with the deconvolution of the serum lipoprotein profile into 110 subfractions, were performed using nuclear magnetic resonance for a quantitative differential analysis comparing the baseline serum samples of responders and non-responders. Results A total of 150 patients were included (30 CD anti-TNF, 30 UC anti-TNF, 30 CD ustekinumab, 30 UC vedolizumab and 30 UC tofacitinib). Metabolomics analysis identified 55 potential predictive biomarkers of IBD treatment response (11 common and 44 drug-specific), with significantly altered levels (p<0.05) in the baseline urine and serum samples of subsequent responders compared to non-responders (Figure 1). Moreover, based on ROC curves, some of these biomarkers showed good sensitivity and specificity for distinguishing between responders and non-responders before treatment (Figure 2). Finally, metabolite set enrichment analysis identified different biological pathways associated with the response to each of the treatments for IBD. Among the common ones, the citrate cycle and the metabolism of butanoate, alanine, aspartate, glutamate, and arginine stood out. Conclusion The present study represents a step towards personalized medicine in the selection of targeted therapies for IBD patients, addressing an important unmet need. Although further validation is needed, we have identified serum and urinary metabolic biomarkers with the potential to predict response to biologic and JAK-inhibitor therapies.

P0643 Development of a personalized infliximab dosing algorithm for Acute Severe Ulcerative Colitis: results of a multi-center pharmacometrics analysis

Abstract Background Acute severe ulcerative colitis (ASUC) is a medical emergency with a potential need for emergency colectomy. Infliximab (IFX) is a safe and effective rescue therapy for patients with steroid-refractory ASUC. Despite being increasingly practiced, there is no evidence that intensified/accelerated IFX regimens are superior to standard induction dosing [1]. However, insight into the IFX pharmacokinetics (PK) and personalized dosing in ASUC are lacking. Methods We performed a multicenter, retrospective population PK (popPK) and exposure–response modeling study using pooled individual data from ASUC patients diagnosed via Truelove and Witts score. Data on IFX dosing, exposure, patient demographics, and treatment outcomes were collected. A popPK model was developed to predict the relationship between IFX dosing and exposure. Parametric time-to-event analysis was used to predict colectomy within 3 months, considering patient characteristics and PK projections. An algorithm for personalized, risk-stratified IFX rescue dosing was developed. Modeling and simulation tasks were performed in NONMEM. Results Eight medical centers contributed data from 74 patients with ASUC (18 female; median [interquartile range] age 33 [22–47] years; body weight 63 [56–75] kg), including 157 IFX concentrations (Table 1). Baseline C-reactive protein (CRP) and serum albumin were 30 [7–87] mg/L and 31 [27–38] g/L, respectively. Eleven patients (15%) underwent colectomy within 90 days after start of IFX therapy. The one-compartmental popPK model with typical IFX clearance (CL) 0.48 L/day (14% relative standard error) and volume of distribution (V) 12.9 L (21%) described the IFX concentration–time data well. IFX CL and V increased with higher body weight. CL increased with higher CRP. The ratio of the Bayesian forecasted (hence simulated) area under the IFX concentration–time curve between weeks 2 and 4 (AUCw2–w4) over the estimated CL (AUCw2–w4/CL), was the best predictor of colectomy (area under the receiver operating characteristic curve, 0.80 [95%CI 0.54–1.00]). The higher the Ln(AUCw2–w4/CL), which we defined as the colectomy index (C-index), the lower the hazard risk for colectomy. A C-index of 5.84 discriminated best between patients with and without colectomy (sensitivity 83%, specificity 84%) (Figure 1). The classification accuracy was 82% [95%CI 71%–91%]. Conclusion We performed the first model-based dose–exposure–response analysis of IFX in patients with ASUC. We developed the C-index as a predictor for colectomy, which combines AUCw2–w4 (modifiable risk factor) and IFX CL (unmodifiable risk factor). Personalized dosing for IFX rescue therapy using individuals’ AUCw2–w4 target is feasible using an early TDM sample and a precision dosing software tool.

P1176 Low serum albumin levels are associated with higher colectomy rates in patients with moderate-to-severe ulcerative colitis on tofacitinib

Abstract Background This study aimed to evaluate the real-world, long-term effectiveness and safety of tofacitinib in a large cohort of patients with refractory or difficult-to-treat ulcerative colitis (UC). Methods A multicentre, retrospective, observational cohort study was conducted, including patients with moderately to severely active UC who received tofacitinib for at least 8 weeks. Outcomes assessed included clinical remission and response, endoscopic response and remission, biochemical response and remission, steroid-free clinical remission, primary and secondary loss of response, drug discontinuation, dose optimisation, the need for colectomy, and adverse events over a follow-up period of up to 30 months. Results The study included 127 patients with UC, with a mean age of 40.3 ± 14.2 years; 58.2% were male, 75.6% had pancolitis, and 79.5% had previously failed at least one biological therapy, predominantly anti-TNF agents (70.1%). Clinical remission was achieved by 31.5% of patients at weeks 12–16, 46.5% at 26 ± 4 weeks, and 37.0% at 1 year. Steroid-free clinical remission was observed in 28.6%, 44.8%, and 37.1% of patients at these respective time points. Biochemical remission occurred in 33.6% of patients at 26 ± 4 weeks and 29.3% at 1 year. Endoscopic response and remission within 1 year were reported in 46.0% and 15.3% of patients, respectively. Ten patients (7.9%) required colectomy, and 13 patients (10.2%) were hospitalised, all of whom had previous exposure to biologics. The colectomy rate was significantly higher in patients with baseline serum albumin levels ≤ 3.5 g/dL (21.4% vs. 4.1%, p = 0.013) (Table 1). Conclusion This large, long-term real-world study demonstrated that tofacitinib effectively induced clinical remission and endoscopic improvement while preventing colectomy for over 30 months in patients with predominantly biologically refractory UC. The safety profile was favourable. However, baseline hypoalbuminemia was associated with higher colectomy rates, highlighting its prognostic significance.

P0494 Serum regenerating islet-derived 3-alpha (REG3α) is a new prognostic biomarker in Crohn’s Disease

Abstract Background Regenerating islet-derived 3-alpha (REG3α) is a serum biomarker that, alone or in combination with ST2 (suppressor of tumorigenesis 2), has been used to risk-stratify patients in primary treatment trials for acute graft-versus-host disease (aGVHD) due to its accurate prediction of 6-month non-relapse mortality (1-3). Serum REG3α reflects Paneth cell function and intestinal stem cell niche integrity (4). Given the similarities between intestinal manifestations of aGVHD and Crohn’s disease (CD), we aimed to evaluate the prognostic value of REG3α in CD. Methods We enrolled 231 patients with CD on the Mount Sinai Crohn’s Colitis Registry (MSCCR) at the time of scheduled endoscopic evaluation. We prospectively collected baseline serum samples, and longitudinal clinical data were extracted from structured electronic health records [Table 1]. We used multivariable logistic regression models to investigate associations of IBD progression events, defined as hospitalization, surgery, steroid course, or new biologic, with baseline REG3α levels, controlling for clinical variables [age, biologic use, surgical history, Montreal classification, C-reactive protein (CRP), and endoscopic disease activity (Simple Endoscopic Score, or SES-CD)]. We derived a cutpoint via Youden’s Index to designate high- and low-risk groups by REG3α and used log-rank tests to uncover any difference in times-to-IBD progression event. Results Adjusting for SES-CD, CRP, and age, serum REG3α levels independently associated with adverse IBD outcomes (aOR 1.88, 95% confidence interval [CI] 1.16-3.04, p=0.01)). In subgroups of patients in endoscopic remission (n=124) or with remission+mild endoscopic disease (n=160), REG3α still significantly associated with IBD progression events (aOR 1.89 (95% CI: 1.05-3.39, p=0.034) for SES-CD<3; aOR 1.84 (95% CI: 1.14-3.00, p=0.013) for SES-CD<7). We used Youden’s index to derive a prognostic REG3α cutpoint of 30.29 ng/mL, with sensitivity 0.63 and specificity 0.62, to identify patients at risk of adverse IBD outcomes. High REG3α above the cutpoint conveyed increased hazards of IBD disease progression events (HR 1.91 (95%CI 1.33-2.75, p<0.001 via log-rank test, Figure 1) at median 6.5 (interquartile range (IQR), 3-8) years of follow-up. Conclusion REG3α has potential as a non-invasive, prognostic biomarker in CD, independent of endoscopic inflammation. Elevated REG3α levels were associated with an increased risk of IBD-related disease progression events, including shorter time until IBD surgery, hospitalization, steroid course, or biologic use. References (1)Ferrara JLM, Harris AC, Greenson JK, et al. Regenerating islet-derived 3-alpha is a biomarker of gastrointestinal graft-versus-host disease. Blood. 2011;118(25):6702-6708. doi: 10.1182/blood-2011-08-375006 (2)Major-Monfried H, Renteria AS, Pawarode A, et al. MAGIC biomarkers predict long-term outcomes for steroid-resistant acute GVHD. Blood. 2018;131(25):2846-2855. doi:10.1182/blood-2018-01-822957 (3)Marafini I, Di Sabatino A, Zorzi F, et al. Serum regenerating islet-derived 3-alpha is a biomarker of mucosal enteropathies. Aliment Pharmacol Ther. 2014;40(8):974-981. doi:10.111/apt.12920 (4)Zhao D, Kim YK, Jeong S, et al. Survival Signal REG3a prevents crypt apoptotsis to control acute gastrointestinal graft-versus-host disease. J Clin Invest. 2018;128(11):4970-4979. doi:10.1172/JCI99261

Regression of carotid atherosclerosis in high-risk individuals with proprotein convertase subtilisin/kexin type 9 inhibitors.

Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors represent a novel approach for reducing cholesterol and, accordingly, the burden of atherosclerosis. However, limited data are available regarding the possible effects of PCSK9 inhibitors on atherosclerotic plaque. To evaluate the efficacy of PCSK9 inhibitors in reducing carotid plaque progression in individuals with high-risk carotid atherosclerotic disease. We used carotid total plaque area (TPA) to assess the burden of atherosclerosis. Ultrasound imaging of the carotid was acquired before and after the initiation of PCSK9 inhibitor therapy. We selected high-risk cases with atherosclerosis with a minimum of three ultrasound examinations, 1 year before, one at the time of initiation of a PCSK9 inhibitor, and 1 year after initiating a PCSK9 inhibitor. Statistical analysis was conducted using the mixed-effects model with Restricted Maximum Likelihood (REML). We reviewed data from 131 patients with a mean follow-up of 6 (±4) years. Patients were high-risk, with the majority having diabetes or hypertension. There was a decrease in TPA, particularly during the first 3 years after initiating PCSK9 inhibitor therapy (p < 0.05). Furthermore, we observed that individuals with higher baseline serum low-density lipoprotein cholesterol (LDL-C) levels experienced a greater decline in TPA (p < 0.05). PCSK9 inhibitors are effective in achieving plaque regression in high-risk patients with atherosclerosis. This is important, as plaque regression is associated with a lower risk of stroke, myocardial infarction, or vascular death.

Association between clinical activity score and serum sPD-1 and sPD-L1 levels during systemic glucocorticoid treatment for active moderate-to-severe thyroid eye disease.

CD4+ T lymphocytes are key immune cells involved in orbital inflammation in thyroid eye disease (TED). Inhibition of their activity is important in treatment of TED, but effective drugs targeting these cells are lacking. The programmed cell death-1/programmed cell death ligand-1 pathway has been implicated in several T-cell-mediated diseases. Manipulation of this pathway with antagonists or agonists is an attractive therapeutic option. The role of soluble programmed cell death-1 (sPD-1) and soluble programmed cell death ligand-1 (sPD-L1) in regulation of this pathway is debated. This study aimed to investigate the involvement of sPD-1 and sPD-L1 in the pathogenesis of TED, focusing on their utility as novel biomarkers to evaluate disease severity and treatment response. Thirty patients diagnosed with moderate-to-severe TED associated with Graves' disease were included. Blood samples were collected from patients before and 12weeks after initiation of intravenous glucocorticosteroid (IVGC) treatment. Disease severity was assessed using the Clinical Activity Score (CAS) before and after IVGC treatment. Thyroid-stimulating hormone, free thyroxine, free triiodothyronine, thyroid-stimulating immunoglobulin, interleukin-6, sPD-1, and sPD-L1 levels were measured. Correlations between sPD-1, sPD-L1, and CAS before and after IVGC treatment were investigated. Serum concentrations of sPD-1 and sPD-L1 before and after IVGC treatment in patients with TED were compared with those in healthy controls (HCs). The changes in the tested protein concentrations upon IVGC treatment and their associations with clinical characteristics were investigated. Enzyme-linked immunosorbent assays were used to measure sPD-1 and sPD-L1 concentrations in peripheral blood serum. There was a positive correlation of moderate Spearman's rank strength between sPD-L1 and CAS before and after treatment, and a positive correlation between sPD-1 and sPD-L1. However, no correlation was observed between sPD-1 and CAS. Baseline serum levels of sPD-1 and sPD-L1 did not significantly differ between patients with TED and HCs. There were no correlations between changes in the levels of the tested molecules upon IVGC treatment and the analyzed clinical features. The decreases of sPD-1 and sPD-L1 levels after 12weeks of IVGC treatment were not significant. The positive correlation of moderate Spearman's rank strength between sPD-L1 and CAS before and after 12weeks of treatment indicates that sPD-L1 is involved in the pathogenesis of TED. sPD-L1 may become an additional immunological biomarker to assess the disease activity and monitor the respond to treatment. Although sPD-1 is reported in the literature to have an activating effect on lymphocytes, our study shows that sPD-1 may not play a significant role in the pathogenesis of TED, as its level does not differ significantly between the TED and HC groups and does not correlate with disease activity. Understanding the clinical value of sPD-1 and sPD-L1 is of great practical importance.

Serum Medium-Chain Fatty Acids and the Risk of Incident Diabetes: Findings From the 4C Study.

Emerging studies have revealed associations between dietary medium-chain fatty acids (MCFAs) and glucose homeostasis. However, the relationship between serum MCFAs and the incidence of diabetes, and potential interactions with genetic predisposition, remains unclear in prospective cohort studies. This work aimed to investigate associations and genetic susceptibility between serum MCFAs and diabetes risk. We investigated baseline serum MCFAs (n = 5) in a nested case-control study comprising incident diabetes cases (n = 1707) and matched normoglycemic control individuals (n = 1707) from the China Cardiometabolic Disease and Cancer Cohort Study. Associations between MCFAs and type 2 diabetes mellitus (T2DM) were examined, both overall and stratified by diabetes genetic susceptibility. Genetic risk scores (GRS) were calculated based on 86 T2DM-associated genetic variants. In the fully adjusted conditional logistic regression model, serum octanoic acid and nonanoic acid exhibited inverse dose-response relationships with diabetes risk, showing odds ratios (95% CI) of 0.90 (0.82-0.98) and 0.84 (0.74-0.95), respectively. Subgroup analysis demonstrated that inverse associations between MCFAs and incident diabetes were more pronounced among individuals with physical inactivity (Pinteraction = .042, .034, and .037, for octanoic, nonanoic and decanoic acid, respectively). Moreover, inverse associations of octanoic acid with diabetes risk were notably enhanced among individuals with high genetic risk compared to those with low genetic risk. Statistically significant interactions were observed between octanoic acid and GRS on T2DM risk (Pinteraction = .003). These findings provide evidence supporting inverse associations between serum MCFAs and T2DM risk, and reveal potential interplay between genetic susceptibility and circulating octanoic acid in modulating diabetes risk.

Baseline Vitamin D Levels on Quality of Life and Pain Perception Among Patients with Chronic Pain with Long-Term Prescription Opioid Use: A Prospective Study.

Objectives: To investigate the correlation between baseline serum concentrations of 25-hydroxyvitamin D (25-OHD) and quality of life (QoL), as well as pain perception in patients with chronic pain with long-term prescription opioid usage before opioid detoxification. Methods: We prospectively studied 45 patients with chronic pain with long-term prescription opioid usage who were selected for elective detoxification. Baseline serum 25-OHD levels were measured prior to detoxification, classifying patients as either vitamin D deficient (<75 nmol/L) or sufficient (≥75 nmol/L). QoL was assessed using the SF-36v2TM questionnaire, while pain levels were assessed using Visual Analogue Scale (VAS) scores before treatment. Results: Mean pain scores before detoxification of the patients with sufficient baseline 25-OHD levels vs. those with deficient levels were, respectively, 6.06 ± 2.32 vs. 6.86 ± 2.10 (normalized scores 1.22 ± 0.571 vs. 0.950 ± 0.632; p = 0.164). The analysis of SF-36v2™ questionnaire scores revealed minimal variation between groups (35.00 ± 14.198 vs. 34.97 ± 13.52), indicating no significant association between Vitamin D levels and QoL (p = 0.913). Conclusions: The analysis of baseline 25-OHD levels in relation to QoL assessments and pain scores did not reveal a statistically significant association, indicating that variations in baseline vitamin D levels may not substantially impact QoL or pain perception. Further studies may help determine how to assess and optimize vitamin D levels in patients with chronic pain on long-term prescription opioids.

Value of serum tryptophan in stratified management of 90-day mortality risk in patients with hepatitis B virus-related acute-on-chronic liver failure: a multicenter retrospective study.

To explore the correlation of serum tryptophan level with 90-day mortality risk in patients with hepatitis B virus-related acute-on-chronic liver failure (HBV-ACLF). This retrospective study was conducted among 108 patients with HBV-ACLF, whose survival outcomes within 90 days after diagnosis were recorded. The correlation of baseline serum tryptophan levels measured by high-performance liquid chromatography with 90-day mortality of the patients was analyzed, and the predictive value of serum tryptophan for 90-day mortality was explored. Within 90 days after diagnosis, 53 (29.4%) of the patients died and 127 (70.6%) survived. The deceased patients had significantly lower baseline serum tryptophan levels than the survivors (7.31±3.73 pg/mL vs 13.32±7.15 pg/mL, P<0.001). Multivariate analysis suggested that serum tryptophan level was an independent factor correlated with mortality of HBV-ACLF after adjustment for confounding variables. The patients with serum tryptophan levels below the median level (10.14 pg/mL) at admission had significantly higher 90-day mortality risks than those with higher tryptophan levels (43.3% vs 15.6%, HR: 3.157, 95% CI: 1.713-5.817), and the complication by kidney dysfunction further increased the risk to 73.3% as compared with patients with higher serum tryptophan levels with normal kidney function (15.0%; HR: 7.558, 95% CI: 3.369-16.960). Serum tryptophan levels had an area under the receiver operating characteristic curve of 0.771 (95% CI: 0.699-0.844) for predicting 90-day mortality. Serum tryptophan level is closely correlated with the survival outcomes of patients with HBV-ACLF, and a decreased tryptophan level indicates a high 90-day mortality risk, which can be further increased by the complication by kidney dysfunction.

Risk factors associated with the failure of local methotrexate combined with minimally invasive surgery for late cesarean scar pregnancy

BackgroundThis study aimed to investigate the risk factors related to the failure of initial combined local methotrexate (MTX) treatment and minimally invasive surgery for late cesarean scar pregnancy (CSP).MethodsThis retrospective case-control study was conducted between January 2016 and December 2023, involving patients with late CSP (≥ 8 weeks) who received local MTX injection combined with either hysteroscopic or laparoscopic surgery. Cesarean scar pregnancy was classified as type I, II, or III based on the direction of growth of the gestational sac and the residual myometrial thickness as assessed by ultrasound. Binary logistic regression analysis was utilized to identify the risk factors associated with the failure of the initial combined treatment.ResultsOverall, 574 patients with late CSP were included in our study. Among them, 29 patients (5.1%) experienced treatment failure with the initial local MTX combined with minimally invasive surgery, while 545 patients (94.9%) achieved successful treatment outcomes. In the univariate analysis, several potential risk factors associated with the initial combined treatment failure were identified, including baseline serum β-human chorionic gonadotropin (β-hCG) levels, type of CSP, time interval between MTX and surgery, and positive fetal heart activity before surgery. Subsequent binary logistic regression analysis revealed the following independent risk factors linked to the failure of the initial combined treatment: baseline serum β-hCG levels exceeding 94,000 IU/L [odds ratio (OR) 3.060, 95% confidence interval (CI) 1.387–6.749, P = 0.006], type III CSP (OR 3.574, 95% CI 1.147–11.135, P = 0.028), a time interval greater than seven days between MTX and surgery (OR 3.847, 95% CI 1.725–8.581, P = 0.001), and the presence of a fetal heartbeat before surgery (OR 4.405, 95% CI 1.014–19.128, P = 0.048).ConclusionThe findings indicate that higher baseline serum β-hCG levels, an extended time interval between MTX and surgery, type III CSP and a positive preoperative fetal heartbeat are significant risk factors for the failure of initial local MTX combined with minimally invasive surgery in patients with late CSP. Individualized treatment strategies are recommended for these high-risk patients with late CSP.

Predicting acute kidney injury in trauma using extreme gradient boosting model: a temporal validation study

Abstract Background Acute kidney injury (AKI) is a significant complication in patients with trauma. The early identification of AKI in these patients poses challenges. This study aimed to predict AKI in trauma patients 24 or 48 hours in advance using an extreme gradient boosting (XGBoost) model. Methods We analyzed 17 859 trauma patients admitted to a regional trauma center between January 2015 and July 2023. Demographic, clinical, and laboratory parameters were collected. The model was developed using data until July 2021 and validated using data from August 2021. We developed models to predict AKI stages 1 to 3 and AKI stages 2 and 3 occurring 48 and 24 h later and measured predictive performance in the validation group. The models' performance was evaluated using the area under the receiver operating characteristic curve (AUROC), and feature importance was assessed through SHapley Additive exPlanations values. Results The study population exhibited an incidence of AKI of 6.6% in the development group and 5.4% in the validation group. The models demonstrated predictive performances with AUROCs of 0.864 and 0.886 for 48-hour predictions of AKI stages 1 to 3 and stages 2 and 3, and 0.904 and 0.903 for 24-hour predictions of AKI stages 1 to 3 and stages 2 and 3, respectively. Key features influencing model predictions included baseline and in-hospital serum creatinine values, injury severity score, age, lactate dehydrogenase, D-dimer, platelets, albumin, and C-reactive protein levels. Conclusions The XGBoost models effectively predicted AKI in trauma patients up to 48 h in advance using clinical data.

Serum stromal cell-derived factor 1α as a prognostic indicator in elderly patients with acute myeloid leukemia receiving CAG-based chemotherapy.

Stromal-cell-derived factor 1 (SDF-1) plays a crucial role in hematopoiesis and has been implicated in acute myeloid leukemia (AML) pathogenesis. Understanding its relationship with chemotherapy outcomes could lead to improved therapeutic approaches for elderly AML patients. This study retrospectively analyzed the medical records of elderly AML patients (n = 187) and compared serum SDF-1α levels with age-matched controls (n = 120). Patients received CAG (cytarabine, aclarubicin, and G-CSF)-based chemotherapy, and serum SDF-1α levels were assessed using ELISA. Serum SDF-1α levels were significantly elevated in elderly AML patients compared to controls (p < 0.001). Receiver operating characteristic (ROC) analysis confirmed its diagnostic relevance, revealing the area under the ROC curve (AUC) of 0.76. Factors such as age, French-American-British (FAB) classification, Eastern Cooperative Oncology Group (ECOG) performance status, primary AML status, white blood cell count, and bone marrow blast cell ratio, were confirmed to be prognostically relevant. Serum SDF-1α levels were elevated in patients who did not achieve complete remission (NCR) compared to those in complete remission (CR). ROC analysis further highlighted the predictive capability of serum SDF-1α for chemotherapy responsiveness. Independent predictors of treatment failure included age, FAB classification, ECOG status, and serum SDF-1α levels. Following chemotherapy, serum SDF-1α levels decreased in patients in CR but remained unchanged in those in NCR. Higher baseline levels of SDF-1α were associated with shorter overall survival. Elevated serum SDF-1α levels in elderly AML patients are associated with poor chemotherapy response and shorter survival. Baseline serum SDF-1α levels could serve as a prognostic marker for CAG-based treatment outcomes.

The Incidence and Outcomes of Acute Kidney Disease in Critically Ill Children.

Acute kidney disease (AKD) includes abnormalities of kidney function present for <90 days. Acute kidney injury (AKI) is defined as a subset of AKD, with onset within seven days. There is scant data on the rates of AKD in children and its association with outcomes. Our primary objective was to examine the rates of AKD with and without AKI and compare major adverse events (MAKE) in children in the pediatric intensive care unit (PICU). This is a retrospective cohort study of patients ≤18 years old who were admitted to a quaternary care PICU between 2009 and 2016 using the high-density pediatric database. All patients included in the primary analysis had a known baseline serum creatinine. Patients who had a baseline estimated glomerular filtration rate (eGFR) <60 ml/min/1.73 m2 or a history of dialysis dependence or kidney transplant were excluded. AKI and AKD were defined by Kidney Disease: Improving Global Outcomes definitions. MAKE-90 was defined as a composite outcome of death, dialysis, or persistent kidney dysfunction 90 days after PICU admission. Among 5,922 children included in this study, 1,199 (20.2%) had AKD, of which 1,092 (91%) had AKD with AKI and 107 (8.9%) had AKD without AKI. MAKE-90 occurred in 26% (308/1,199) of those with AKD compared to 3.6% (172/4723) without (p=<0.001). MAKE-90 occurred in 26% (279/1,092) of AKD with AKI and 27% (29/107) of AKD without AKI. After adjusting for age, sex, and illness severity, compared to patients that had no AKD, patients with AKD with AKI (aOR: 14.39, 95% CI: 11.06-18.72) and patients with AKD without AKI (aOR: 7.83, 95% CI: 4.54-13.51) had a greater odds of MAKE-90. More than a quarter of pediatric critically ill patients with AKD develop MAKE-90. Even in the absence of AKI, AKD is an independent risk factor for MAKE-90.

The Interactive Effects of Fruit Intake Frequency and Serum miR-484 Levels as Biomarkers for Incident Type 2 Diabetes in a Prospective Cohort of the Spanish Adult Population: The Di@bet.es Study.

Background/Objectives: Although evidence suggests that miR-484 and several fruit components are involved in glucose metabolism and insulin resistance metabolic pathways, the relationship between serum miR-484 levels and fruit consumption in relation to the risk of Type 2 diabetes (T2DM) remains elusive. The aim of this study was to evaluate the possible association between serum miR-484 levels and fruit intake frequency with the risk of T2DM in the Spanish adult population. Methods: 2234 subjects from the Di@bet.es cohort study without T2DM at baseline were studied. Socio-demographic, anthropometric and clinical data were recorded, as well as responses to a questionnaire on habits, including frequency of fruit consumption (daily vs. occasional). T2DM was diagnosed at baseline and after 7.5 years of follow-up. Baseline serum miR-484 levels were measured using real-time qPCR and categorized based on the 25th percentile. Association analyses were performed using logistic regression models adjusted for potential confounders. Interaction effects were evaluated on the multiplicative and additive scales. Results: There was no association between miR-484 levels and fruit intake frequency. Categorized miR-484 levels and fruit consumption were inversely and independently associated with the likelihood of incident T2DM. Analysis of the interaction effect suggests the presence of both positive multiplicative and additive interactions between miR-484 categories and fruit consumption frequency. Conclusions: Our study demonstrates a protective effect of daily fruit intake and high miR-484 levels regarding the risk of T2DM and supports the nutritional recommendations advocating daily fruit consumption. This study also suggests that the combined effect of low miR-484 levels and occasional fruit intake may increase the risk of T2DM beyond their independent effects.

Kidney function, bone health, and vascular calcifications in patients with CKD II - IV: A 2 - 3 year prospective study with bone biopsies.

Patients with chronic kidney disease (CKD) have serum, bone, and vascular abnormalities presenting as chronic kidney disease-mineral bone disorder (CKD-MBD) syndrome. This study sought to identify the parameters with the greatest relative impact on progression of CKD-MBD abnormalities. This prospective study measured 237 parameters including serum markers, clinical variables, dual-energy X-ray absorptiometry (DXA) measurements, vascular calcifications, and histomorphometric results from bone samples obtained at baseline and after 2-3 years. Relative impact of these parameters on kidney function, bone changes, and vascular calcification were assessed using machine learning, a subset of artificial intelligence analyses. Baseline estimated glomerular filtration rate (eGFR) values ranged from 18 to 70 mL/min and declined in 52% of subjects by at least 3.3% annually during the study. These declines in eGFR were associated with changes in specific serum markers, bone quantity decreases, and bone quality alterations, but not with arterial calcifications. Arterial calcifications were associated with collagen crosslinking heterogeneity, serum phosphorus, diuretics and atorvastatin treatment, but not with kidney function. Baseline collagen crosslinking heterogeneity was an important factor impacting progression of coronary, but not aortic calcification. Baseline serum phosphorus was a factor primarily associated with progression of aortic calcification. Machine learning revealed specific bone and vascular abnormalities occurring early during loss of kidney function. Bone, vascular, blood, medication use, and other parameters were identified impacting the presence and progression of arterial calcification and altering bone quality and quantity in this understudied patient population. Serum phosphorus levels considered normal impacted progression of arterial calcification. Identification of these parameters and their relative importance enhances our understanding of CKD progression and should improve patient care.

Mechanistic implications of the Mediterranean diet in patients with newly diagnosed Crohn's disease- multi-omic results from a prospective cohort.

To decipher the mechanisms underlying the protective role of the Mediterranean diet (MED) in Crohn's disease (CD), we explored the implications of adherence to MED on CD course, inflammatory markers, microbial and metabolite composition. Patients with newly diagnosed CD were recruited and followed prospectively. MED adherence was assessed by repeated food frequency questionnaires (FFQ), using a predefined IBDMED score, alongside validated MED adherence screeners. Crohn's disease activity index (CDAI), C-reactive protein (CRP), fecal calprotectin and microbial composition (16S-rRNA-sequencing) were assessed each visit. Baseline serum and fecal samples were analyzed for targeted quantitative metabolomics. Consecutive patients: 271 (52% males, average age- 31±12 years, B1 phenotype- 75%). FFQ collected: 636 (range 1-5 FFQ per patient). Adherence to MED was associated with a non-complicated CD course, and inversely correlated with CDAI, fecal calprotectin, CRP and microbial dysbiosis index (all P < .05). Increasing adherence to MED over time correlated with reduced CDAI and inflammatory markers (P < .05). Adherence to MED correlated with a microbial cluster of commensals and short-chain fatty acid producers including Faecalibacterium, and with plant metabolites, vitamin derivatives and amino acids. Conversely, adherence to MED inversely correlated with a cluster of oral genera, Escherichia coli and Ruminococcus gnavus, known CD-associated species, and with tryptophan metabolites, ceramides and primary bile acids (FDR < .2). Adherence to MED is associated with beneficial clinical outcomes and decreased inflammatory markers. These may be driven by lower levels of primary bile-acids and microbial dysbiosis and a beneficial microbial and metabolite composition. Randomized controlled trials are needed to evaluate the role of MED in CD management.

Protective role of apolipoprotein A and B in Parkinson's disease: A prospective study from UK Biobank.

Evidence have indicated relation between apolipoproteins and neurodegenerative disorders (NDDs). However, previous studies have produced inconsistent results, and a comprehensive analysis of apolipoproteins in NDDs is currently lacking. Using Cox proportional hazards regression analysis based on data from UK Biobank, we examined the association between baseline serum levels of apolipoprotein A (ApoA) and apolipoprotein B (ApoB) and risk of Parkinson's disease (PD), Alzheimer's disease, amyotrophic lateral sclerosis, frontotemporal dementia, and multiple sclerosis. Elevated baseline levels of serum ApoA (HR=0.84, 95% CI: 0.71-0.99, P=0.047) and ApoB (HR=0.67, 95% CI: 0.57-0.78, P=3.18E-07) were associated with a reduced risk of incident PD. Subgroup analyses suggested the protective effect of serum ApoA was more significant for older participants and those with lower alcohol consumption, while higher serum ApoB was a more significant protective factor in males and those without stroke. No significant associations were found between apolipoproteins and other NDDs. Increased baseline levels of serum ApoA and ApoB are linked to a lower risk of PD. These findings enhance understanding of the role of apolipoproteins in PD, and have implications for the development of therapeutic strategies in clinical trials.

Impact of Hyponatraemia at Clinical Stable-State on Survival in Patients with Chronic Obstructive Pulmonary Disease.

Hyponatraemia has been suggested to be associated with morbidity and mortality among various medical disorders. Evidence on the association between stable-state hyponatraemia and prognosis in patients with chronic obstructive pulmonary disease (COPD) is lacking. All COPD patients followed up in a regional hospital in year 2015 were included, with their clinical outcomes reviewed in the subsequent eight years. Association between stable-state hyponatraemia and mortality was evaluated. Stable-state hyponatraemia is defined as baseline serum sodium levels, at least 90 days away from the last AECOPD <135mmol/L. There were 271 COPD patients included. Hyponatraemia was associated with shorter overall survival with adjusted hazard ratio (aHR) 1.74 (95% CI = 1.07-2.65, p = 0.026). The median overall survival was 3.05 years (95% CI = 2.65-3.46) for patients in the hyponatraemia group, in contrast to 3.35 years (95% CI = 2.86-3.83) for those without hyponatraemia. The highest baseline serum sodium levels were significantly negatively associated with annual acute exacerbation of COPD (AECOPD) and annual hospitalized AECOPD frequency in the follow-up period, with Pearson correlation coefficient of -0.16 (p = 0.011) and - 0.14 (p = 0.027), respectively. Stable-state hyponatraemia was associated with increased mortality and probably AECOPD frequency among patients with COPD.

Association of baseline cytokines with antibody concentrations after diphtheria-tetanus-acellular pertussis booster vaccination in Finnish children

BackgroundDespite extensive vaccinations, pertussis remains endemic and epidemic in multiple countries. The persistence of cases can be partly attributed to the significant individual variation in vaccine responses. This study evaluated the association of baseline cytokines (before booster vaccination) on antibody concentrations to Tdap-vaccine antigens. MethodsHealthy Finnish children (7–10y, n = 36), adolescents (11–15y, n = 37), young adults (20–34y, n = 25), and older adults (60–70y, n = 23) received a Tdap3-IPV booster. Serum antibodies against pertussis toxin (PT), filamentous hemagglutinin (FHA), pertactin (Prn), fimbriae 2/3, diphtheria toxoid (DT), and tetanus toxoid (TT), as well as PT neutralizing antibodies were measured before, one month, and one year after the booster. Baseline serum concentrations of IFN-γ, IL-2, IL-5, IL-10, IL-13, IL-17 A and IL-17F were determined. ResultsThe proportion of detectable and undetectable baseline cytokines varied between age groups 58.3 % of children had a higher proportion of detectable IL-5, IL-10, IL-13, and IL-17F compared to adolescents (IL-5, 37.8 %; IL-10, 48.6 %; IL-13, 48.6 %; IL-17F, 37.7 %), young adults (IL-5, 36.0 %; IL-10, 28.0 %; IL-13, 36.0 %; IL-17F, 44.0 %), and older adults (IL-5, 26.1 %; IL-10, 21.7 %; IL-13, 39.1 %; IL-17F, 30.4 %). IFN-γ had a lower detectability in children (44.4 %) and young (40.0 %) and older adults (39.1 %) in contrast to adolescents (62.2 %). IL-2 was undetectable in all age groups while the proportion of detectable IL-17 A decreased with age. A mixed model showed that undetectable baseline levels of IFN-γ, IL-2, IL-10, and IL-17 A were associated with higher antibody concentrations in children before and after vaccination, particularly against PT. Positive associations were observed in adolescents for anti-TT concentrations and young adults for anti-FHA IgA concentrations. ConclusionThese findings indicate a possible role of existing cytokines in pertussis booster antibody concentrations in children and warrant further studies in different populations. However, the results should be interpreted with caution as the number of subjects is limited.