Marker Of Disease Severity Research Articles

Cerebrospinal Fluid Calcium Balance in Tick-Borne Encephalitis: A Preliminary Study and Future Research Directions

Introduction: Calcium homeostasis is essential for neurophysiological functions, with dysregulation implicated in neurodegenerative diseases. Recent studies suggest that specific viral brain infections, such as tick-borne encephalitis, can initiate neuronal loss and subsequent neurodegenerative changes. This study examines alterations in calcium levels within the cerebrospinal fluid (CSF) of patients with tick-borne encephalitis (TBE). Objectives: To evaluate the concentration of calcium in the CSF of TBE patients and assess its potential as a diagnostic marker for disease severity. Materials and Methods: CSF samples were collected from 42 subjects (11 controls, 20 with TBE, 11 with other forms of meningitis). Calcium levels were measured using the Alinity c analyzer. Statistical analyses included the Shapiro–Wilk test, Mann–Whitney U test, and ROC curve analysis. Results: Calcium levels were significantly lower in TBE patients compared to controls (mean 0.85 mmol/L vs. 0.98 mmol/L). Lower calcium levels were associated with milder cases of TBE. ROC analysis (AUC 0.802, p-value 0.0053) supports the diagnostic utility of calcium concentration in differentiating TBE severity. The optimal cut-off value for calcium was >3.09 mg/dL, with a sensitivity of 84.62% and specificity of 71.43%. These findings further emphasize the potential of calcium as a diagnostic marker for TBEV. Conclusions: The observed differences in CSF calcium levels between mild and severe TBE cases highlight its potential as a diagnostic marker. Further research is warranted to elucidate calcium’s role in TBE, aiming to improve clinical management and reduce complications. We emphasize that this study is one of the first to propose calcium levels as a potential biomarker for assessing the severity of tick-borne encephalitis, offering a new perspective in the diagnostic approach to this infection.

Severe Liver-Related Outcomes in Patients With Hepatitis Delta: Results From a Multi-Ethnic Multicenter Long-Term Follow-Up Study.

Hepatitis B virus (HBV)-hepatitis delta virus (HDV) coinfection is the most severe form of chronic viral hepatitis, but the factors that determine disease progression and severity are incompletely characterised. This long-term follow-up study aims to identify risk factors for severe liver-related outcomes. In this multicentre national cohort study, data from admission until the last visit between 2001 and 2023 was retrospectively collected from 162 HBV-HDV coinfected patients. The inclusion criteria were HBsAg or HBV DNA positivity, anti-HDV or HDV RNA positivity, and at least one follow-up visit. The median follow-up was 6.2 years (IQR 3.3-10.2). At baseline, 68/152 (44.7%) patients were diagnosed with advanced liver fibrosis. Forty patients (24.7%) had at least one severe liver-related outcome during follow-up. HDV viremia was detectable in 92 patients (64.3%) at last evaluation and was more frequently detectable in patients of European origin (p < 0.001). HDV RNA-positive patients had a 4.7-fold higher risk for severe liver-related outcomes (p < 0.001) and were more frequently diagnosed with advanced fibrosis at baseline (p = 0.007) compared to HDV RNA-negative patients. Multivariate analyses identified HDV RNA positivity, as well as several markers for liver disease severity, such as INR, platelet count, and advanced fibrosis at baseline, and age at admission as independent risk factors for severe liver-related outcomes. In conclusion, almost one in four HBV-HDV coinfected patients developed a severe liver-related outcome during follow-up. Several markers for liver disease severity and HDV RNA positivity were the strongest predictors for outcomes.

Nucleated red blood cells for characterization of systemic inflammatory response syndrome in dogs.

Nucleated red blood cells (nRBCs) are increased by disease processes and hematopoietic stress. To evaluate the utility of nRBCs as a marker of disease severity and prognosis in dogs with systemic inflammatory response syndrome (SIRS). Sixty-two client-owned dogs met the criteria of SIRS without anemia. nRBC-positive (nRBCs: ≥5/500, n = 32) and nRBC-negative (nRBCs: <5/500, n = 30) dogs were classified, and clinicopathological data, Acute Patient Physiologic and Laboratory Evaluation (APPLEfast) scores, cytokines, 2- and 4-weeks survival were compared. The median WBC (17.63, interquartile range [IQR]: 11.72-20.24 × 109/L), neutrophils (12.28, IQR: 7.17-16.88 × 109/L), band neutrophils (1288.5, IQR: 252.5-2575 cells/μL), serum IL-6 (731.80, IQR: 299.79-5522.05 pg/mL), and plasma C-reactive protein (4.10, IQR: 1.00-8.58 mg/L) were significantly higher in nRBC-positive dogs than negative dogs (11.27, IQR: 7.63-15.13 × 109/L; 7.57, IQR: 4.96-11.71 × 109/L; 62.5, IQR: 0-350.25 cells/μL; 232.30, IQR: 99.33-447.01 pg/mL; 0.40, IQR: 0.10-3.00 mg/L, respectively; P < .05). The median reticulocyte count (87.95, IQR: 52.45-130.55 × 103/μL) and serum IL-3 (40.94, IQR: 29.85-53.52 ng/L) were also significantly greater in nRBC-positive dogs than nRBC-negative dogs (46.00, IQR: 26.43-68.15 × 103/μL; 25.24, IQR: 21.65-37.40 ng/L, respectively; P < .01). The presence of circulating nRBCs, but not the reticulocyte count, at admission was predictive of death in dogs with SIRS at 2 weeks (P = .01, AUC: 0.729) and 4 weeks (P = .002, AUC: 0.731). The overall survival time was shorter in nRBC-positive dogs (95% CI, 47.35-113.90) than nRBC-negative dogs (95% CI, 90.92-135.55; P = .03). Measuring peripheral nRBCs in dogs with SIRS is rapid and clinically applicable, reflecting disease severity and associated prognosis.

Urine Neutrophil Gelatinase-Associated Lipocalin in Non-Associative Immune Mediated Hemolytic Anemia: A Prospective Controlled Study in 22 Dogs.

Urine neutrophil gelatinase-associated lipocalin (uNGAL) is a biomarker for the early diagnosis of AKI. To evaluate uNGAL in dogs with non-associative immune mediated hemolytic anemia (IMHA) and to evaluate whether uNGAL correlates with disease severity markers, negative prognostic indicators and outcome. Twenty-two dogs with non-associative IMHA and 14 healthy dogs. Prospective case-control study. uNGAL was measured by a commercially available ELISA-kit and corrected to urine creatinine (uNGAL to creatinine ratio [UNCR]). uNGAL and UNCR of IMHA cases were compared to that of healthy dogs and the correlation with other clinicopathological markers was evaluated. uNGAL and UNCR were also compared between dogs with a CHAOS or ASA score < 3 and ≥ 3. uNGAL and UNCR were significantly higher in dogs with IMHA when compared to healthy controls (uNGAL median 114.58 and 0.43 ng/mL, respectively, p < 0.001; UNCR median 174.87 and 0.13 ng/mg, respectively, p < 0.001). uNGAL and UNCR were moderately positively correlated with urea (p = 0.005, r = 0.58, 0.20-0.81 95% CI and p = 0.001, r = 0.64, 0.29-0.84 95% CI, respectively) and total bilirubin (p = 0.003, r = 0.60, 0.22-0.82 95% CI and p = 0.002, r = 0.62, 0.25-0.83 95% CI, respectively). These were also significantly higher in dogs with hemoglobinuria compared to those without (uNGAL: median 269 and 30.99 ng/mL, respectively, p < 0.001; UNCR: median 585.3 and 352 37.47 ng/mg, respectively, p < 0.001). There was no statistically significant difference in uNGAL or UNCR when assessing survival to discharge (p = 0.24 and p = 0.16, respectively, 95% CI). This study suggests that renal injury might be underappreciated in dogs with IMHA.

Circulating cell-free DNA as a potential biomarker for prediction of disease activity and prognosis among Egyptian rheumatoid arthritis patients.

Cell-free DNA (cfDNA) has emerged as a potential biomarker for assessing disease activity and prognosis in rheumatoid arthritis (RA). However, the association between cfDNA levels and the established RA markers of inflammation and disease severity remains unclear. The current study aimed to detect plasma levels of cfDNA in patients with RA and to investigate their association with RA activity indicators (erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), disease activity score-28 (DAS28)), prognostic markers (rheumatoid factor (RF), anticitrullinated protein antibodies (ACPA)), and the musculoskeletal ultrasonographic (US7) scores. This controlled cross-sectional study included 108 RA patients and 108 healthy controls. Plasma levels of cfDNA were quantified by real-time PCR using ALU repeats. Levels of ESR, CRP, RF, and ACPA were measured using routine laboratory assays. Synovial inflammation and joint damage evaluation was performed using the US7 scoring system. Plasma levels of cfDNA were higher in RA patients than controls (P < 0.001) and significantly increased with higher DAS28 scores among all RA activity groups. Also, cfDNA levels were significantly positively correlated with ESR, CRP, RF, and ACPA levels (P-values <0.001). Regarding US7, cfDNA was significantly positively correlated with synovitis and erosion scores (P-values <0.05) but did not correlate significantly with tenosynovitis scores (P-values >0.05). In addition, plasma cfDNA was significantly higher in seropositive RA patients than in seronegative patients (P = 0.007). The odds ratio for cfDNA as a risk factor for erosions was 2.254. This study revealed that cfDNA levels are elevated in RA patients and positively associated with disease activity indicators and prognosis markers. Further research is warranted to validate these findings in larger cohorts and explore the clinical implications of cfDNA measurement in RA management.

Clinical significance of right ventricular - pulmonary arterial uncoupling in hypertrophic cardiomyopathy

Abstract Background Right ventricular (RV) – pulmonary arterial (PA) coupling represents the relationship between RV function and the afterload in the pulmonary vascular system. It is a non-invasive surrogate on how the RV is adapted to an increased afterload in the pulmonary circulation. In cases of exhaustion of compensatory RV remodeling, the ratio decreases and there is RV-PA uncoupling. Several studies reported the usefulness of this parameter in patients with heart failure, including in preserved ejection fraction. There is no evidence regarding the association between RV-PA coupling and hypertrophic cardiomyopathy (HCM). We aimed to evaluate this parameter in patients with HCM. Methods This prospective cohort study enrolled patients with HCM without obstructive epicardial coronary artery disease, that underwent a comprehensive evaluation. Echocardiography was used to assess RV-PA coupling as the ratio of tricuspid annular plane systolic excursion (TAPSE) to pulmonary artery systolic pressure (PASP). In addition, coronary flow reserve in the left anterior descending artery (CFR_LAD) was also evaluated: diastolic coronary flow velocity was measured in basal conditions and in hyperemia and CFR was calculated as the ratio of hyperemic and basal peak diastolic flow velocities. This was used as a surrogate marker of coronary microvascular dysfunction. Functional capacity was evaluated by cardiopulmonary exercise testing (CPET). Cardiac magnetic resonance (CMR) was also performed to evaluate RV function (volumes and ejection fraction), and the extent of late gadolinium enhancement (LGE) in the left ventricle (LV). Results We enrolled 62 patients, with a mean age of 55 (15) years, 64% males. In 64% it was an asymmetrical septal hypertrophy phenotype, in 31% an apical hypertrophy, and in 27%, it was an obstructive HCM. Mean TAPSE/PASP was 0.556 (0.23) and median was 0.50. All patients had a normal LV ejection fraction. TAPSE/PASP showed a modest predictive accuracy for peak VO2 &amp;lt; 20 ml/Kg/min, a marker of decreased functional capacity (AUC 0.671, 95% CI 0.535 – 0.807, p=0.022), with the best cut-off set at 0.60 (sensitivity 85% and specificity 47%). By univariable linear regression analysis, peakVO2 was correlated with age, male gender, E/E’, indexed left atrial volume, indexed right ventricle end-systolic and end-diastolic volumes, CFR_LAD and TAPSE / PASP. The HCM phenotype or the presence of obstruction were not associated with peakVO2. Multivariable stepwise linear regression analysis showed that the independent predictors of peakVO2 were male gender (b-estimate: 0.305, p=0.002), age (b-estimate: - 0.323, p=0.002), RV indexed end-diastolic volume (b-estimate: 0.200, p=0.043) and TAPSE/PASP (b-estimate: 0.275, p=0.005). Conclusion In patients with HCM, RV-PA uncoupling is associated with a reduction in functional capacity. Therefore, it is a marker of disease severity.

Microvascular dysfunction contributes to atrial fibrillation in hypertrophic cardiomyopathy, a multimodality study

Abstract Background Microvascular dysfunction (MVD) constitutes one of the most important pathophysiological features in hypertrophic cardiomyopathy (HCM). Chronic and recurrent myocardial ischemia potentially contributes to arrhythmic risk, namely to atrial fibrillation (AF). Purpose To analyze the impact of MVD in the occurrence of AF in HCM patients (P), assessed by coronary flow velocity reserve (CFVR) on echocardiography (echo) and ischemia on cardiovascular magnetic resonance (CMR). Methods Prospective study, which enrolled HCM P without obstructive epicardial coronary artery disease, who underwent stress echo and stress CMR. By echo, the evaluation of CFVR in the left anterior descending (LAD) artery was performed in apical three chambers view. Diastolic coronary flow velocity was measured in basal conditions and in hyperemia, induced by adenosine perfusion (0.14 mg/kg/min intravenously, during 2 minutes). CFVR was calculated as the ratio of hyperemic to basal peak diastolic flow velocities. On CMR, perfusion imaging was acquired during regadenoson-induced hyperemia. To quantify the ischemic burden, the myocardium was divided into 32 subsegments (16 AHA segments subdivided into an endocardial and epicardial layer, excluding segment 17) and the ischemic burden was calculated as the number of involved subsegments, assigning 3% of myocardium to each subsegment. Late gadolinium enhancement (LGE) was quantified used the 6 standard deviation method. Kaplan Meyer curves were performed to evaluate the impact of CFVR, ischemia, left atrial volume and LGE in the occurrence of atrial fibrillation during the follow up. Results 73P were enrolled, 47 (64%) males, mean age 54.3(14.8) years. 19 P (26%) had obstructive HCM, mean maximal wall thickness (MWT) was 20.1(4.6)mm, left ventricular (LV) mass 96.9(30.6)g/m2, LV ejection fraction 71.6(8.4)%, left atrial volume (LAV) 47.0(16.8)ml/m2, CFVR LAD 1.8(0.4), ischemic burden 22.5(17.1)% of LV. During the follow up of 54.6(7.8) months (minimum 42months, maximum 80months), P with more severe microvascular dysfunction (CFVR LAD&amp;lt;2.0 and ischemia ≥18% of LV) had significant higher incidence of atrial fibrillation (figure 1). P with CFVR LAD≥2.0 and LAV≤34ml/m2 had significantly less AF comparing to P with CFVR LAD&amp;lt;2.0 and LAV&amp;gt;34ml/m2. Interestingly, P with only one of this risk factors had similar incidence of AF, pointing toward a similar impact of microvascular dysfunction and LA dilatation. Although LGE is a well-known surrogate marker of disease severity, extension of the ischemia seemed to play a more important role in AF development, as patients with ischemia ≥ 18% of LV and LGE &amp;lt; 15% had more AF than P with ischemia &amp;lt; 18% of LV and LGE ≥ 15%. Conclusion Microvascular dysfunction and consequent ischemic burden were linked to AF, which likely reflects advanced disease, involving atrial myocardium beyond LV myocardium, contributing for atrial dysfunction and arrhythmogenicity. Figure 1

Differentiating Kawasaki Disease and Multisystem Inflammatory Syndrome in Children Using Blood Composite Scores: Insights into Clinical Outcomes and Predictive Indices.

The study sought to assess the clinical utility of complete blood count-derived composite scores, suggesting their potential as markers of inflammation and disease severity in Kawasaki disease (KD) and multisystem inflammatory syndrome in children (MIS-C) with Kawasaki-like features. This retrospective study analyzed data from 71 KD and 73 MIS-C patients and 70 healthy controls. The KD group showed a higher rate of coronary involvement (26.7% vs. 10.9%), while the MIS-C group had a higher intensive care unit (ICU) admission rate (34.2% vs. 2.8%). Platelet counts, lymphocyte counts, mean platelet volume (MPV), MPV/Lymphocyte (MPVLR), and MPV/Platelet (MPVPR) ratios demonstrated the highest specificities in distinguishing MIS-C than KD (84.5%, 83.1%, 91.1%, 88.7%, and 88.7%, respectively). Monocyte counts, MPV, and MPVPR demonstrated the highest specificities to predictive ICU admission in the MIS-C group (83.3%, 89.6%, and 89.6%, respectively). Lymphocyte counts, platelet/lymphocyte ratio (PLR), neutrophil/lymphocyte ratio (NLR), MPVLR, and Systemic Immune-Inflammation Index (SII) parameters were found to have high negative predictive values for predicting KD patients without coronary artery lesions (CALs) (85.7%, 86.1%, 87.1%, 87.1%, and 85.7%, respectively)., Systemic Inflammation Response Index (SIRI), MPVPR, and CRP were independently predictive of ICU admission in the MIS-C group, and lymphocyte count and IVIG resistance were also identified as significant predictors of CALs in the KD group. NLR, MPVLR, MPVPR, and NPR indices effectively differentiate MIS-C from KD and predict ICU admission in MIS-C. NLR, PLR, MPVLR, and SII are valuable in excluding CALs in KD with high negative predictive values. In addition, SIRI and MPVLR were independent predictors of ICU admission in MIS-C, and lymphocyte count was identified as an independent predictor of CALs in KD.

Occurrence and clinical correlates of SARS-CoV-2 viremia in two German patient cohorts

Viremia defined as detectable SARS-CoV-2 RNA in the blood is a potential marker of disease severity and prognosis in COVID-19 patients. Here, we determined the frequency of viremia in serum of two independent COVID-19 patient cohorts within the German National Pandemic Cohort Network (German: Nationales Pandemie Kohorten Netzwerk, NAPKON) with diagnostic RT-PCR against SARS-CoV-2. A cross-sectional cohort with 1,122 COVID-19 patients (German: S ektorenuebergreifende Platform, SUEP) and 299 patients recruited in a high-resolution platform with patients at high risk to develop severe courses (German: H ochaufloesende Plattform, HAP) were tested for viremia. Our study also involved a comprehensive analysis and association of serological, diagnostic and clinical parameters of the NAPKON medical dataset. Prevalence of viremia at the recruitment visit was 12,8% (SUEP) and 13% (HAP) respectively. Serological analysis revealed that viremic patients had lower levels of SARS-CoV-2 specific antibodies as well as lower neutralizing antibodies compared to aviremic patients. Viremia was associated with severity (<0.0001 SUEP; 0.002 HAP) and mortality of COVID-19 (both cohorts <0.0001) compared to aviremic patients. While rare, viremia was also detected in patients with mild disease (0.7%). In patients of the SUEP cohort with acute kidney disease (p = 0.0099) and hematooncological conditions (p = 0.0091), viremia was detected more frequently. Compared to the aviremic group, treatment with immunomodulating drugs as well as elevated levels of inflammatory markers in the blood was more frequent in the viremic group. In conclusion, our analysis revealed that detectable viremia correlates with hyperinflammatory conditions and higher risk for severe COVID-19 disease.

Gut Microbes as the Major Drivers of Rheumatoid Arthritis: Our Microbes Are Our Fortune!

Rheumatoid arthritis (RA) is an autoimmune disease with an unknown etiology. While certain genes provide strong susceptibility factors, the role of environmental factors is becoming increasingly recognized. Among genetic factors, human leukocyte antigen (HLA) genes, encoded within the major histocompatibility complex (MHC), have been linked to predisposition to RA, while among environmental factors, smoking, infections and diet are the major contributors. Genetic and environmental factors impact microbial composition in the host. Based on the dysbiosis observed in the gut and lung microbiome, a mucosal origin of RA has been suggested. However, proving whether genes or microbes provide a stronger risk factor has been difficult. Studies from RA patients and various mouse models, specifically humanized mice expressing HLA class II genes, have been instrumental in defining the role of environmental factors such as smoking and endogenous small intestinal microbes in modulating arthritis severity. The consensus based on most studies support an interaction between host genetic and environmental factors in the onset and severity of disease. However, until now, no microbial markers for disease prognosis or treatment efficacy have been available. Here, the role of gut microbes as markers of disease severity, and the potential for using endogenous commensals for modulating immune responses to suppress inflammation in the context of genetic factors, are discussed.

P0073 Evaluation of PYGL as a Biomarker and Therapeutic Target in Ulcerative Colitis

Abstract Background Inflammation begins when innate immune cells recognize and respond to infections or tissue injuries to protect the body. In particular, cells such as macrophages and dendritic cells require more energy to manage these conditions. Glycogen metabolism is a crucial function for cells recruited to the site of inflammation to obtain energy. Within that process, glycogen phosphorylase plays a pivotal role as an enzyme for glycogenolysis. Because ulcerative colitis (UC) is a long-term condition in which the colon and rectum become inflamed, patients with the disease might have high levels of protein or activity of glycogen phosphorylase (PYGL) in the blood. Therefore, this study aims to identify the protein level and activity of PYGL in the serum and peripheral blood mononuclear cells (PBMC) of ulcerative colitis patients. Methods After blood from UC patients was provided by Daejeon St. Mary's Hospital, the PBMCs were isolated using Leucosep tube pre-filled with separation medium (Greiner bio-one, 163288), and the serum was isolated by centrifugation at 1000 x g for 10 minutes in a refrigerated centrifuge (Labogene, 1248R). The PBMCs were stored in an LN2 cell storage tank (ICBiomedical, LS6000), and the serum was stored in a deep freezer (Nihon freezer, CLN-52UW) at -80°C until samples of 60 patients were gathered. To compare with UC patients, normal human PBMCs (STEMCELL Technologies, 70025.1) were used. PYGL levels in serum and PBMCs from normal and UC patients were measured using Human PYGL ELISA Kit (Colorimetric) (Novus, NBP2-82520). PYGL activity in serum and PBMCs from normal and UC patients were measured using Glycogen phosphorylase activity assay kit (Colorimetric) (Abcam, ab273271). Activity Vmax and level from serum and PBMCs were analyzed using an unpaired t-test to determine significant differences (p &amp;lt; 0.05), fitting the standard. Activity reaction curve from serum and PBMCs was anlyzed using an mutiple unpaired t-test to determine significant differences (q &amp;lt; 0.05). GraphPad Prism 10 software was used for all analysis and the data were presented as Mean and SEM. Results Significant differences in PYGL activity were observed between UC patients and healthy controls in both serum and PBMC samples, though PYGL levels did not exhibit notable variation. These findings support the hypothesis that PYGL activity is linked to UC pathology and may serve as a marker for disease severity and progression. Conclusion This study provides initial evidence that PYGL activity could be a predictive biomarker and therapeutic target in UC. Future studies are warranted to further elucidate its role and assess the potential of PYGL inhibitors as a treatment strategy for autoimmune and inflammatory conditions like UC. References Ji Q, Li H, Cai Z, Yuan X et al. Share PYGL-mediated glucose metabolism reprogramming promotes EMT phenotype and metastasis of pancreatic cancer. Int J Biol Sci. 2023 Mar 21;19(6):1894-1909. Ma J, Wei K, Liu J et al. Glycogen metabolism regulates macrophage-mediated acute inflammatory responses. Nat Commun. 2020 Apr 14;11(1):1769. Roach PJ, Depaoli-Roach AA, Hurley TD, Tagliabracci VS. Glycogen and its metabolism: some new developments and old themes. Biochem J. 2012 Feb 1;441(3):763-87. Thwe PM, Pelgrom LR, Cooper R et al. Cell-Intrinsic Glycogen Metabolism Supports Early Glycolytic Reprogramming Required for Dendritic Cell Immune Responses. Cell Metab. 2019 Jul 2;30(1):225.

Sphingosine-1-Phosphate, a Marker of Endothelial Injury and Disease Severity in Preeclampsia.

Preeclampsia is a hypertensive pregnancy disorder marked by endothelial damage. Healthy endothelium is covered by a protective glycocalyx layer, which, when degraded, releases detectable products into the blood. Sphingosine-1-phosphate (S1P) is a cardiovascular biomarker involved in glycocalyx preservation, linked to placentation and preeclampsia development. The study aimed to test the hypothesis that plasma S1P is altered alongside glycocalyx degradation products in severe preeclampsia compared with controls. We included 121 females: 41 with severe preeclampsia requiring treatment in the intensive care unit, 40 with preeclampsia but no need of intensive care unit treatment, and 40 with normotensive pregnancies. Plasma levels of S1P and glycocalyx degradation products-hyaluronic acid, SDC-1 (syndecan-1), and HSPG2 (heparan sulfate proteoglycan-2)-were analyzed from blood samples taken within 27 hours postpartum. Postpartum plasma S1P was significantly lower in the intensive care unit cohort compared with both preeclampsia controls and normotensive controls (P<0.001). Hyaluronic acid and SDC-1 levels were elevated in the intensive care unit group versus normotensive controls (P=0.009 and P=0.023), while HSPG2 was lower (P<0.001). Plasma S1P correlated with hyaluronic acid and blood pressure. Intensive care patients with severe preeclampsia have lower plasma S1P levels and higher concentrations of glycocalyx degradation products, indicating more pronounced endothelial damage. These findings suggest that S1P is associated with preeclampsia severity and may serve as a biomarker to assess vascular damage in this patient population. Further studies are needed to explore the potential role of S1P in long-term cardiovascular risk assessment for patients with preeclampsia.

P0184 Molecular signature of bowel urgency in Ulcerative Colitis

Abstract Background Bowel urgency is a ‘top three’ symptom of concern to patients with ulcerative colitis (UC), but the mechanisms are unclear [1]. Determining the molecular signatures of bowel urgency would reveal targetable mechanisms and generate measurable endpoints for future use. Methods Clinical data from the Oxford University Hospitals real world cohort were analysed. Oxford patient-reported Simple Clinical Colitis Activity Index (SCCAI) scores (including bowel urgency scale 0-3) were extracted from the TrueColours-IBD remote monitoring platform [2], which includes 2,186 patients with UC. Contemporaneous routinely scored endoscopic (UCEIS) and histological (Nancy index) activity were extracted from medical records. Molecular RNA-sequencing (RNAseq) signatures were generated from diagnostic biopsies. Results Overall, bowel urgency showed weak-to-moderate correlations (Spearman correlation coefficient &amp;lt;0.4) with clinical laboratory (CRP, albumin and haemoglobin), endoscopic (UCEIS) and histological (Nancy histologic index) measures of disease activity. By contrast, bowel urgency correlated moderately-to-strongly (Spearman correlation coefficient &amp;gt;0.6) with most other patient-reported symptom measures (bowel frequency, general wellbeing and total SCCAI). Based on bulk RNAseq profiling from biopsies of patients with UC obtained within two weeks of a reported SCCAI, we defined molecular signatures of cellular contractility, lymphocyte activation, B cell immunity and chemotaxis. Molecular signatures that most strongly correlated with objective markers of inflammation (such as endoscopic and histological measures) were also correlated with reported bowel urgency [FIGURE 1]. However, there were notable cases of discordance between urgency and objective measures of inflammation [FIGURE 2]. Conclusion At a cohort level, bowel urgency correlates with laboratory, endoscopic and histological measures of UC, but most strongly correlates with other patient reported symptoms indicative of disease activity. In corroboration, at a molecular RNA-level, bowel urgency similarly correlates with endoscopic and histologic markers of disease severity. However, on a patient-level there is a notable subset of patients with UC who demonstrate discordance between patient-reported urgency and objective markers of inflammation. Together, this suggests the presence of both overlapping and non-overlapping mechanisms of the symptomatic experience of urgency and bowel inflammation, which we are dissecting at a cellular level.

Retinal Vessels Whitening in Retinitis Pigmentosa.

To characterize retinal vessel whitening (RVW) in Retinitis Pigmentosa (RP). Single-center cross-sectional study. Review of clinical notes of clinically confirmed RP patients was performed followed by grading ultra-widefield imaging. Data collected included Best corrected visual acuity (BCVA), presence or absence and location of RVW and were correlated with disease. In total, 120 RP patients' charts were reviewed. Of these, 116 patients (232 eyes) were included in the final analysis with a mean age of 43.2 (39.8, 46.6) and a 1:1 male to female ratio. RVW was seen in either eye of 44 (38%) subjects, most frequently in the inferotemporal quadrant (p< 0.001). Total retinal thickness within the ETDRS area was significantly less in eyes with RVW (p<0.001), a mean difference of 151.7 µm. Both the inner and outer retina were thinner in the RVW group (p<0.001). There was also a significant association (p<0.04) between the number of quadrants of the retina affected by RVW and the reduction in retinal thickness. RVW is a common finding in RP, suggesting that it should be considered as a phenotypic feature of RP. RVW is also associated with structural changes to the central macula indicating its potential use as a marker of retinal disease severity.

Tremor as an intrinsic feature of juvenile myoclonic epilepsy.

We aim to understand whether tremor may be an intrinsic feature of juvenile myoclonic epilepsy (JME) and whether individuals with JME plus tremor experience a different disease course. Thirty-one individuals with JME plus tremor (17 females, mean age = 33.9 ± 13.8 years) and 30 age of onset- and gender-matched subjects with JME (21 females, mean age = 26.8 ± 11.2 years) prospectively underwent clinical and neurophysiologic assessment, including tremor assessment and somatosensory evoked potentials (SEPs). All JME plus tremor subjects experienced postural and action tremor affecting bilateral upper limbs. Nine of 31 individuals (29%) with tremor were never exposed to valproate (VPA), and 14 of 31 (45.2%) were not using VPA at the time of clinical evaluation. Twelve of 31 (38.7%) patients with JME plus tremor were drug-resistant compared to four of 30 (13.3%) with JME (p = .024). The JME plus tremor subjects had higher numbers of previous childhood absence epilepsy (n = 6/31 [19.4%]), interictal epileptiform discharges (n = 30/31 [96.8%]), photosensitivity (n = 8/31 [25.8%]), and psychiatric comorbidities (n = 12/31 [38.7%]). Six of 31 (19.4%) individuals with JME plus tremor had giant SEPs (1/30, 3.3% with JME; p = .05, chi-squared test). The clinical features and decreased sensorimotor inhibition in the JME plus tremor group suggest that tremor might be a marker of disease severity rather than an epiphenomenon of VPA exposure.

Identification of Key Predictors of Cryoglobulinemia Severity at Diagnosis: Threshold, Type, and Severity Score at Diagnosis.

Background: Cryoglobulinemia (CG) syndrome is a heterogeneous condition characterized by the presence of cryoglobulins in serum, often leading to vasculitis with protean clinical manifestations. Understanding the presentation of cryoglobulinemia-related symptoms based on cryoprecipitate levels, GC type, and severity at diagnosis is essential for effective management. Hence, this study aimed to provide a comprehensive analysis of patients with positive cryoglobulin detection to investigate these aspects. Methods: We conducted a retrospective review of clinical charts from patients with positive cryoglobulin detection at Colmar Hospital between May 2015 and April 2019. Results: Among 166 patients with positive cryoglobulins, the median cryoprecipitate value was 37 mg/L [IQR: 25-70], with 62% of patients below the 50 mg/L threshold. High cryoprecipitate levels were associated with C-virus hepatitis (p = 0.0007), increased fatigue (p = 0.001), fever (p = 0.0013), weight loss (p = 0.028), and musculoskeletal symptoms (p = 0.002). These patients also exhibited decreases in complement fractions (p-values 0.017 to 0.006). At the end of the one-year follow-up, they required frequent renal replacement therapy (p < 0.0001) and had a higher mortality rate (p = 0.02). Based on the CG type, patients with type I GC had splenomegaly (p = 0.039) and hemopathy (p = 0.001). According to severity at initial presentation, the severe patients had more purpura (p < 0.001), Raynaud's phenomenon (p = 0.039), and leukocytoclastic vasculitis on skin biopsy (p < 0.001), along with higher cryoprecipitate levels (p = 0.011). Multivariate analysis identified purpura (OR: 10.25), hematological malignancy (OR: 7.06), Raynaud's phenomenon (OR: 6.41), and cryoprecipitate levels (OR: 1.02) as significant markers of disease severity serving for the development of a severity score for clinical practice. Conclusions: This study identifies severity markers in patients with positive cryoprecipitate and proposes a score related to severity at diagnosis.

Pathology of Red Blood Cells in Patients with SARS-CoV-2.

Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has been associated with various hematological disorders. Understanding the pathology of erythrocytes (red blood cells) in coronavirus infection may provide insights into disease severity and progression. Objective: To review and analyze the general pathology of erythrocytes in patients infected with SARS-CoV-2, focusing on clinical and laboratory findings across different severity groups. Methods: Patients were classified into four groups based on clinical criteria: Group 1: Regular group (fever, respiratory symptoms, and radiographic evidence of pneumonia). Group 2: Severe group (shortness of breath >30 breaths/min, peripheral blood oxygen saturation <92% at rest, extensive pneumonia, respiratory failure requiring mechanical ventilation, and/or organ failure necessitating intensive care). Group 3: Low saturation group (peripheral blood oxygen saturation <85% at rest). Group 4: Erythroblastosis group (erythroblast count >0.5% among total nucleated blood cells). Clinical laboratory investigations included major routine studies and scanning microspectrophotometry to measure hemoglobin (Hb) spectra in unstained erythrocytes. Results: Erythroblasts were detected in approximately 30% of SARS-CoV-2 patients, predominantly in the severe group. Serum ferritin, C-reactive protein (CRP), and anisocytosis were strongly correlated with disease severity. Microspectrophotometric studies revealed significant changes in hemoglobin adsorption spectra, with an increase in Hb absorbance at 420 nm in severe cases compared to normal controls. Conclusions: Elevated serum ferritin, CRP levels, anisocytosis, and altered hemoglobin absorption at 420 nm wavelength are associated with adverse outcomes in SARS-CoV-2 infection. These findings highlight the potential utility of hematological parameters as markers for disease severity and prognosis in viral infections.

Evaluation of the Mucin Glycoprotein (KL‑6) as a Prognostic Factor in COVID‑19 Patients

Lung damage caused by SARS-CoV-2 infection has been described in the literature as resulting from direct cytopathic effects on type II pneumocytes, playing a critical role in the extent and progression of pulmonary injury. This study aimed to evaluate the prognostic value of the mucin glycoprotein KL-6 in predicting clinical outcomes in COVID-19 patients. We prospectively enrolled 260 COVID-19 patients admitted to specialized hospitals in Naples under the ASL Napoli 1 Centro between March 20, 2020, and March 31, 2022, when the state of emergency ended. Our institution, part of the Coronet Lab network designated by the Campania Region and the Ministry of Health, performed 203,368 molecular tests for COVID-19 during this period, identifying 17,650 positive cases (8.67%). The study cohort had a median age (IQR) of 63 years (54–72), comprising 199 males and 61 females. All patients underwent clinical, radiological, and functional assessments in the emergency department. Serum KL-6 levels were measured at admission, after detecting interstitial lung damage, and during hospitalization. Elevated KL-6 concentrations were observed in patients with pulmonary abnormalities, and baseline levels demonstrated good accuracy in identifying those with radiologically documented fibrotic sequelae. In hospitalized COVID-19 patients, serum KL-6 levels also correlated with severe cases requiring mechanical ventilation and predicted the development of fibrotic lung sequelae during follow-up. Finally, KL-6 proved to be an effective predictive marker of disease severity, emphasizing its potential role in guiding clinical management and prognosis.

Bronchiolitis Severity Affects Blood Count and Inflammatory Marker Levels: A Real-Life Experience.

Bronchiolitis is the most common cause of lower respiratory tract infection (LRTI) in the first year of life. We analyzed the association between complete blood count (CBC), c-reactive protein (CRP), and novel inflammatory indexes (NLR, PLR, MLR, ELR, LMR, NPR, LPR, LNR, PNR, SII, SIRI) in predicting bronchiolitis severity at hospital admission. We retrospectively collected data from 95 infants hospitalized for bronchiolitis in a third-level hospital during three epidemic seasons. Five outcomes of severity were analyzed: BRAS; pediatric intensive care unit (PICU) admission; ventilatory support; intravenous (IV) rehydration; and length of stay (LOS). Lower age and weight at admission were statistically associated with four of the five severity outcomes. Prolonged LOS (≥6 days) was associated with high values of total white blood cells, lymphocytes, and eosinophils. Only three inflammatory indexes (PLR, MLR, and PNR) showed a significant association with one outcome (prolonged LOS). A new index (RBC/AiW/1000) was statistically associated with each severity outcome for a value > 350. We proposed a comprehensive analysis of the association between CBC, CRP, and novel inflammatory indexes and bronchiolitis severity. RBC/AiW/1000 could represent a future predictive marker of disease severity at hospital admission in infants with bronchiolitis.

High-throughput proteomics identifies inflammatory proteins associated with disease severity and genetic ancestry in patients with hidradenitis suppurativa.

Hidradenitis Suppurativa (HS) is a chronic inflammatory skin condition with a greater prevalence and disease burden in patients who identify as African American and those with a family history of HS, suggesting a strong genetic component to its pathogenesis. To evaluate the relationship between plasma inflammatory protein expression, HS disease severity, and genetic ancestry in a diverse cohort of patients with Hidradenitis Suppurativa. We performed a case-control study of patients with HS compared to age-, sex-, and ethnicity-matched healthy controls. We profiled circulating inflammatory proteins using Olink High-throughput proteomics and determined genetic ancestry from whole-genome sequencing data. Using linear regression, we identified novel proteins associated with HS after adjusting for age, sex, and ethnicity. Our analysis also revealed differences in the inflammatory proteome linked to disease severity. Specifically, we found that plasma IL6 levels can distinguish between different Hurley stages, indicating that IL6 may serve as a marker of disease severity. Additionally, we observed variations in inflammatory protein levels based on genetic ancestry: patients with predominantly African ancestry exhibited higher levels of inflammatory proteins associated with neutrophilic inflammation, while those with predominantly European ancestry showed increased levels of Th1-related inflammatory proteins. Single-center study. Limited sample size. Unable to account for treatment status or comorbidities that may influence the level of inflammatory cytokines. Genetic ancestry and disease severity influence the plasma inflammatory profile in patients with HS.