Biomarkers Of Disease Severity Research Articles

Serum CCL24 as a Biomarker of Fibrotic and Vascular Disease Severity in Systemic Sclerosis.

Systemic sclerosis (SSc) is a heterogeneous disease, characterized by variable tissue and vascular fibrosis in the context of autoimmune activation. CCL24 (or Eotaxin2) has been shown to promote microangiopathic, proinflammatory, and profibrotic processes in preclinical models of SSc. Here, we study serum CCL24 levels in a real-life cohort of patients with SSc, to determine its distribution across disease features and its value in predicting disease progression and related mortality. Serum CCL24 was assessed in an observational cohort of consecutively enrolled patients with SSc. A high CCL24 cutoff was defined based on its distribution in a matched cohort of healthy controls. Disease progression and mortality were analyzed from the date of serum assessment. Two-hundred thirteen consecutively enrolled patients with SSc were included in this analysis. Median disease duration was six years (interquartile range 3-14), 28.6% of patients presented with interstitial lung disease (ILD), 46.9% had digital ulcers, and 25.3% showed high CCL24 serum concentration. High-CCL24 patients were more frequently male and positive for anti-scl-70, with a diagnosis of ILD and synovitis (P < 0.05 for all). Notably, high-CCL24 patients had lower diffusion of carbon monoxide and higher prevalence of digital ulcers, telangiectasias, and calcinosis (P < 0.05 for all). In a longitudinal setting, high CCL24 was associated with greater lung function decline and with higher disease-related mortality. Serum CCL24 is a biomarker of disease severity across fibrotic and vascular disease manifestations. These data support the development of therapies targeting CCL24 as a novel comprehensive therapeutic target in SSc.

Association between decreased cord blood inter-alpha inhibitor levels and neonatal encephalopathy at birth

BackgroundInter-alpha inhibitor proteins (IAIPs) are structurally related proteins found in the systemic circulation with immunomodulatory anti-inflammatory properties. Reduced levels are found in inflammatory related conditions including sepsis and necrotizing enterocolitis, and in neonatal rodents after exposure to hypoxia ischemia. In the current study, cord blood IAIP levels were measured in neonates with and without exposure to hypoxic-ischemic encephalopathy (HIE). MethodsThis is a prospective cohort study including infants born ≥36 weeks over a one-year period. Term pregnancies were divided into two groups: a “reference control” (uncomplicated term deliveries), and “moderate to severe HIE” (qualifying for therapeutic hypothermia). IAIPs were quantified using a sensitive ELISA on the cord blood samples. ResultsThe study included 57 newborns: Reference control group (n = 13) and moderate/severe HIE group (n = 44). Measurement of IAIP cord blood concentrations in moderate to severe HIE group [278.2 (138.0, 366.0) μg/ml] revealed significantly lower IAIP concentrations compared with the control group [418.6 (384.5, 445.0) μg/ml] (p = 0.002). ConclusionsThese findings suggest a potential role for IAIPs as indicators of neonates at risk for HIE. IAIP levels could have diagnostic implications in the management of HIE. Future research is required to explore the relationship between HIE and IAIPs as biomarkers for disease severity. Category of studyTranslational.

Revisiting the pathophysiology of intracranial hemorrhage in fetuses with Chiari II malformation - novel imaging biomarkers of disease severity?

Intracranial hemorrhage (ICH) has emerged as a notable concern in Chiari II malformation (CM II), yet its origins and clinical implications remain elusive. This study aims to validate the in-utero prevalence of ICH in CM II and investigate contributing factors, and visualize the findings in a network format. A single-center retrospective review of fetal MRI scans obtained in fetuses with CM II presenting (January 2007 to December 2022) was performed for ICH utilizing EPI-T2* blood-sensitive sequence. Fetuses with aqueduct stenosis (AS) were included as a control group. The incidence of ICH and corresponding gestational ages were compared between CM II and AS cases, and morphometric measurements (inner/outer CSF spaces, posterior fossa, venous structure) were compared among the four 1:1 age-matched groups: CM II+ICH, CM II-ICH, AS+ICH, and AS-ICH. Additionally, a co-occurrence network was constructed to visualize associations between phenotypic features in ICH cases. A total of 101 fetuses with CM II and 90 controls with AS at a median gestational age of 24.4 weeks and 22.8 weeks (P=.138) were included. Prevalence of ICH in fetuses with CM II was higher compared to the AS cases (28.7% vs 18.9%, P=.023), accompanied by congested veins (deep vein congestion mainly in young fetuses, and cortical veins may also be affected in older fetuses). ICH was notably correlated with specific anatomical features, essentially characterized by reduced outer cerebrospinal fluid spaces and clivus-supraocciput angle. The co-occurrence network analysis reveals complex connections including bony defects, small posterior fossa dimensions, vermis ectopia, reduced CSF spaces as well as venous congestion and venous sinus stenosis as pivotal components within the network. The high prevalence of ICH - detected by fetal MRI -among fetuses with CM emphasizes the pathophysiological importance of venous congestion, ICH, and vasogenic edema. As indicators of disease severity, these features may serve as helpful additional imaging biomarkers for the identification of potential candidates for fetal surgery.ABBREVIATIONS: CM II＝Chiari type II malformation; AS＝aqueduct stenosis; ICH ＝Intracranial hemorrhage.

Elevated serum uric acid in asymptomatic primary hyperparathyroidism: a biomarker of disease severity?

Elevated serum uric acid in asymptomatic primary hyperparathyroidism: a biomarker of disease severity?

Assessment of symptom severity in psychotic disorder patients based on heart rate variability and accelerometer mobility data

Background:Advancement in mental health care requires easily accessible, efficient diagnostic and treatment assessment tools. Viable biomarkers could enable objectification and automation of the diagnostic and treatment process, currently dependent on a psychiatric interview. Available wearable technology and computational methods make it possible to incorporate heart rate variability (HRV), an indicator of autonomic nervous system (ANS) activity, into potential diagnostic and treatment assessment frameworks as a biomarker of disease severity in mental disorders, including schizophrenia and bipolar disorder (BD). Method:We used a commercially available electrocardiography (ECG) chest strap with a built-in accelerometer, i.e. Polar H10, to record R-R intervals and physical activity of 30 hospitalized schizophrenia or BD patients and 30 control participants through ca. 1.5-2 h time periods. We validated a novel approach to data acquisition based on a flexible, patient-friendly and cost-effective setting. We analyzed the relationship between HRV and the Positive and Negative Syndrome Scale (PANSS) test scores, as well as the HRV and mobility coefficient. We also proposed a method of rest period selection based on R-R intervals and mobility data. The source code for reproducing all experiments is available on GitHub, while the dataset is published on Zenodo. Results:Mean HRV values were lower in the patient compared to the control group and negatively correlated with the results of the PANSS general subcategory. For the control group, we also discovered the inversely proportional dependency between the mobility coefficient, based on accelerometer data, and HRV. This relationship was less pronounced for the treatment group. Conclusions:HRV value itself, as well as the relationship between HRV and mobility, may be promising biomarkers in disease diagnostics. These findings can be used to develop a flexible monitoring system for symptom severity assessment.

Neurofilament light chain is elevated in patients with newly diagnosed idiopathic intracranial hypertension: A prospective study.

Idiopathic intracranial hypertension is a secondary headache disorder potentially causing visual loss. Neurofilament light chain is a candidate, prognostic biomarker, but further studies of neuronal biomarkers are needed. Our objective was to investigate neurofilament light chain in cerebrospinal fluid (cNfL) and plasma (pNfL), amyloid-beta 42 (Aβ-42), total-tau and phosphorylated-tau in cerebrospinal fluid in new-onset idiopathic intracranial hypertension. Prospective case-control study including new-onset idiopathic intracranial hypertension and age, sex and BMI matched controls. Biomarkers were compared between patients and controls and related to papilledema, visual fields and opening pressure. We included 37 patients and 35 controls. Patients had higher age-adjusted cNfL (1.4 vs. 0.6 pg/mL, p-adjusted < 0.001), pNfL (0.5 vs. 0.3 pg/mL, p-adjusted < 0.001) and total-tau/Aβ-42 (0.12 vs. 0.11, p-adjusted = 0.039). Significant, positive linear correlations were found between cNfL, pNfL, total-tau/Aβ-42 and opening pressure. Patients with severe papilledema had elevated cNfL compared to mild-moderate papilledema (median cNfL: 4.3 pg/mL (3.7) versus 1.0 pg/mL (1.4), p-adjusted = 0.009). cNFL was inversely associated with perimetric mean deviation (r = -0.47, p-adjusted < 0.001). cNfL, pNfL and total-tau/Aβ-42 were elevated in new-onset idiopathic intracranial hypertension. cNfL was associated with severity of papilledema and visual field defects at diagnosis. This indicates early axonal damage. Neurofilament light chain is a candidate biomarker for disease severity.

Depletion of retinol-binding protein 4 levels in hospitalized patients with COVID-19: A potential biomarker for disease severity

Depletion of retinol-binding protein 4 levels in hospitalized patients with COVID-19: A potential biomarker for disease severity

P151 Nailfold capillaroscopy for prediction of novel severe organ involvement and mortality in systemic sclerosis

Abstract Background/Aims Nailfold capillaroscopy (NFC) has been suggested as a potential biomarker of disease severity in systemic sclerosis (SSc). Several studies report the association between capillary loss and disease severity however, the association of NFC abnormalities with novel severe organ involvement/progression and mortality in SSc has not been evaluated. We aim to evaluate the association of nailfold capillaroscopy (NFC) abnormalities with novel major organ involvement/progression and mortality in SSc. Methods Follow-up data from patients with SSc registered between 2000 and 2022 were analyzed. Patients underwent NFC at baseline. Baseline demographic data, antibody status, baseline pulmonary function, novel severe organ involvement/progression and mortality were registered. Novel organ involvement/progression was defined as new or progressive involvement of peripheral vasculature, lungs, heart, skin, gastrointestinal, kidney, musculoskeletal at 12 and 24 months of follow-up. The following NFC parameters were evaluated: capillary density, hemorrhages, enlarged and giant capillaries, avascular areas, organization of capillary architecture and scleroderma pattern (early/active/late). Logistic regression modelling was run to assess associations between NFC and clinical parameters, the occurrence of novel severe organ involvement and/or progression and mortality. Results 113 patients were included: 28 (25%) were male, 86 (76%) lcSSc and 27 (23%) dcSSc. 70 patients (61%) developed novel overall severe organ involvement/progression and 40 patients died (36%) during follow-up. Table 1 and table 2 summarizes the associations between NFC and novel severe organ involvement/progression and mortality during follow-up. Loss of capillary density was associated with overall severe organ involvement (p = 0.002), peripheral vascular involvement (p = 0.03), new ILD (p = 0.04) and skin progression (p = 0.01); avascular areas were associated with overall severe organ involvement (p = 0.03), new ILD (p = 0.03) and progression of ILD (p = 0.02) and scleroderma pattern was associated with overall severe organinvolvement (p = 0.03), peripheral vascular involvement (OR p = 0.04), new ILD (p = 0.004), progression of ILD (p = 0.03) and skin progression (p = 0.04). Mortality was associated with ILD (OR 2.56 CI 95% 1.5-7.2, p 0.04), DLCO &amp;lt;70% (2.34 CI 93% 1.42-6.23, p 0.03), a late pattern in NFC (3.42 95% CI 1.42-7.25, p 0.002), presence of hemorrhages (OR 1.77 95% CI 1.24-8.23, p0.034) and avascular zones (OR 6.22 95% CI 2.54-10.3, p 0.021). Survival rates from diagnosis at 10 years were lower in patients with NFC with active a late pattern (40% and 20%) compared with those with normal, unspecific and early pattern (100%, 90% and 70%) (p = 0.008 by log rank test) (figure 1). Conclusion NFC may be a potential biomarker in SSc for predicting novel severe organ involvement and/or progression and mortality. Abnormal capillary density, avascular areas and scleroderma pattern are predictors of overall severe organ involvement, peripheral vascular involvement, novel and progression of ILD and skin progression. Disclosure C. Sieiro Santos: None. P. Pérez García: None. J. Ordas Martínez: None. C. Álvarez Castro: None. E. Díez Álvarez: None.

Angiopoietin-2 associates with poor prognosis in Moyamoya angiopathy.

Moyamoya angiopathy (MA) is a rare cerebrovascular disorder characterized by recurrent ischemic/hemorrhagic strokes due to progressive occlusion of the intracranial carotid arteries. The lack of reliable disease severity biomarkers led us to investigate molecular features of a Caucasian cohort of MA patients. The participants consisted of 30 MA patients and 40 controls. We measured cerebrospinal fluid (CSF) levels of angiogenic/inflammatory factors (ELISA). We then applied quantitative real-time PCR on cerebral artery specimens for expression analyses of angiogenic factors. By an immunoassay based on microfluidic technology, we examined the potential correlations between plasma protein expression and MA clinical progression. A RNA interference approach toward Ring Finger Protein 213 (RNF213) and a tube formation assay were applied in cellular model. We detected a statistically significant (p < 0.000001) up-regulation of Angiopoietin-2 (Ang-2) in CSF and stenotic middle cerebral arteries (RQ >2) of MA patients compared to controls. A high Ang-2 plasma concentration (p = 0.018) was associated with unfavorable outcome in a subset of MA patients. ROC curve analyses indicated Ang-2 as diagnostic CSF biomarker (>3741 pg/mL) and prognostic plasma biomarker (>1162 pg/mL), to distinguish stable-from-progressive MA. Consistently, MA cellular model showed a significant up-regulation (RQ >2) of Ang-2 in RNF213 silenced condition. Our results pointed out Ang-2 as a reliable biomarker mirroring arterial steno-occlusion and vascular instability of MA in CSF and blood, providing a candidate factor for patient stratification. This pilot study may pave the way to the validation of a biomarker to identify progressive MA patients deserving a specific treatment path.

Elevated serum HE4 levels as a novel biomarker of disease severity and hepatic fibrosis in autoimmune hepatitis

BackgroundHuman epididymis protein 4 (HE4) has been identified as a biomarker for renal fibrosis. This study aimed to evaluate the role of HE4 in the diagnosis and determination of disease severity and hepatic fibrosis in autoimmune hepatitis (AIH). MethodsSerum HE4 levels were determined via electrochemiluminescence immunoassays in 60 healthy controls and 109 AIH patients (43 without liver cirrhosis and 66 with liver cirrhosis). Liver biopsy was performed on 56 of 109 enrolled patients. We conducted a 5-year follow-up survey of 53 enrolled patients. All continuous variables were reported as median (25th–75th percentile). ResultsSerum HE4 levels were significantly elevated in autoimmune hepatitis with liver cirrhosis (AIH-LC) patients compared with AIH patients and healthy controls [98.60 (74.15–139.08) vs 73.50 (59.88–82.00) vs 48.75 (43.38–52.93) pmol/L, p = 0.004]. The serum HE4 levels showed a positive correlation with the METAVIR scoring system in patients with liver biopsy (r = 0.711, p < 0.001). Serum HE4 levels were significantly elevated in Child–Pugh class C patients compared with Child–Pugh class B patients and Child–Pugh class A patients [106.50 (83.46–151.25) vs 110.00 (73.83–166.75) vs 77.03 (72.35–83.33) pmol/L, p = 0.006]. The diagnostic sensitivity and specificity of serum HE4 for evaluating liver cirrhosis were 69.7 % and 79.07 %, respectively, with a cutoff value of 82.34 pmol/L in enrolled patients. The logistic regression analysis showed that high levels of HE4 (≥82.34 pmol/L) were associated with AIH-LC (OR = 8.751, 95 % CI = 1.412–54.225, p = 0.020). The Kaplan-Meier curves demonstrated that high levels of serum HE4 (≥82.34 pmol/L) were associated with poor outcome (log-rank p = 0.037, HR = 0.372, 95 % CI = 0.146–0.946). ConclusionsSerum HE4 levels were found to be elevated in AIH-LC patients and exhibited a strong correlation with the severity of hepatic fibrosis, thus supporting their potential clinical value as a novel biomarker of disease severity and hepatic fibrosis in AIH.

Multiparametric magnetic resonance imaging of the liver and spleen in Gaucher disease.

To assess liver and spleen characteristics of a population with Gaucher disease (GD) using multiparametric MRI and MR elastography (MRE) for evaluation of diffuse liver and spleen disease, which includes liver fat fraction, liver and spleen volume and iron deposition, and liver and spleen stiffness correlated with DS3 Severity Scoring System for Gaucher disease (GD-DS3). We prospectively evaluated 41 patients with type 1 Gaucher disease using a 3.0T MRI and MRE between January 2019 and February 2020. Clinical, laboratory, and imaging data was collected. Mann-Whitney, Kruskal-Wallis, and Spearman's correlation were applied to evaluate liver and spleen MRI and MRE, clinical and laboratory variables, and GD-DS3. ERT and SRT treatment groups were compared. Hepatomegaly was seen in 15% and splenomegaly in 42% of the population. Moderate and strong and correlations were found between liver and spleen iron overload (rho = 0.537; p = 0.002); between liver and spleen volume (rho = 0.692, p < 0.001) and between liver and spleen stiffness (rho = 0.453, p = 0.006). Moderate correlations were found between liver stiffness and GD-DS3 (rho = 0.559; p < 0.001) and between splenic volume and GD-DS3 (rho = 0.524; p = 0.001). The prevalence of hepatosplenomegaly, liver fibrosis, and liver iron overload in treated patients with GD is low, which may be related to the beneficial effect of treatment. Liver MRE and splenic volume correlate with severity score and may be biomarkers of disease severity.

Role of auto-antibodies in the mechanisms of dengue pathogenesis and its progression: a comprehensive review.

A complex interaction among virulence factors, host-genes and host immune system is considered to be responsible for dengue virus (DENV) infection and disease progression. Generation of auto-antibodies during DENV infection is a major phenomenon that plays a role in the pathophysiology of dengue hemorrhagic fever and dengue shock syndrome. Hemostasis, thrombocytopenia, hepatic endothelial dysfunction, and autoimmune blistering skin disease (pemphigus) are different clinical manifestations of dengue pathogenesis; produced due to the molecular mimicry of DENV proteins with self-antigens like coagulation factors, platelets and endothelial cell proteins. This review elaborately describes the current advancements in auto-antibody-mediated immunopathogenesis which inhibits coagulation cascade and promotes hyperfibrinolysis. Auto-antibodies like anti-endothelial cell antibodies-mediated hepatic inflammation during severe DENV infection have also been discussed. Overall, this comprehensive review provides insight to target auto-antibodies that may act as potential biomarkers for disease severity, and a ground for the development of therapeutic strategy against DENV.

Wiskott-Aldrich syndrome: a study of 577 patients defines the genotype as a biomarker for disease severity and survival

AbstractWiskott-Aldrich syndrome (WAS) is a multifaceted monogenic disorder with a broad disease spectrum and variable disease severity and a variety of treatment options including allogeneic hematopoietic stem cell transplantation (HSCT) and gene therapy (GT). No reliable biomarker exists to predict disease course and outcome for individual patients. A total of 577 patients with a WAS variant from 26 countries and a median follow-up of 8.9 years (range, 0.3-71.1), totaling 6118 patient-years, were included in this international retrospective study. Overall survival (OS) of the cohort (censored at HSCT or GT) was 82% (95% confidence interval, 78-87) at age 15 years and 70% (61-80) at 30 years. The type of variant was predictive of outcome: patients with a missense variant in exons 1 or 2 or with the intronic hot spot variant c.559+5G>A (class I variants) had a 15-year OS of 93% (89-98) and a 30-year OS of 91% (86-97), compared with 71% (62-81) and 48% (34-68) in patients with any other variant (class II; P < .0001). The cumulative incidence rates of disease-related complications such as severe bleeding (P = .007), life-threatening infection (P < .0001), and autoimmunity (P = .004) occurred significantly later in patients with a class I variant. The cumulative incidence of malignancy (P = .6) was not different between classes I and II. It confirms the spectrum of disease severity and quantifies the risk for specific disease-related complications. The class of the variant is a biomarker to predict the outcome for patients with WAS.

Integrated Analysis Identified TGFBI as a Biomarker of Disease Severity and Prognosis Correlated with Immune Infiltrates in Patients with Sepsis.

Sepsis is a major contributor to morbidity and mortality among hospitalized patients. This study aims to identify markers associated with the severity and prognosis of sepsis, providing new approaches for its management and treatment. Data were mined from the Gene Expression Omnibus (GEO) databases and were analyzed by multiple statistical methods like the Spearman correlation coefficient, Kaplan-Meier analysis, Cox regression analysis, and functional enrichment analysis. Candidate indicator' associations with immune infiltration and roles in sepsis development were evaluated. Additionally, we employed techniques such as flow cytometry and neutral red staining to evaluate its impact on macrophage functions like polarization and phagocytosis. Twenty-eight genes were identified as being closely linked to the severity of sepsis, among which transforming growth factor beta induced (TGFBI) emerged as a distinct marker for predicting clinical outcomes. Notably, reductions in TGFBI expression during sepsis correlate with poor prognosis and rapid disease progression. Elevated expression of TGFBI has been observed to mitigate abnormalities in sepsis-related immune cell infiltration that are critical to the pathogenesis and prognosis of the disease, including but not limited to type 17 T helper cells and activated CD8 T cells. Moreover, the protein-protein interaction network revealed the top ten genes that interact with TGFBI, showing significant involvement in the regulation of the actin cytoskeleton, extracellular matrix-receptor interactions, and phagosomes. These are pivotal elements in the formation of phagocytic cups by macrophages, squaring the findings of the Human Protein Atlas. Additionally, we discovered that TGFBI expression was significantly higher in M2-like macrophages, and its upregulation was found to inhibit lipopolysaccharide-induced polarization and phagocytosis in M1-like macrophages, thereby playing a role in preventing the onset of inflammation. TGFBI warrants additional exploration as a promising biomarker for assessing illness severity and prognosis in patients with sepsis, considering its significant association with immunological and inflammatory responses in this condition.

Assessing brain involvement in Fabry disease with deep learning and the brain-age paradigm.

While neurological manifestations are core features of Fabry disease (FD), quantitative neuroimaging biomarkers allowing to measure brain involvement are lacking. We used deep learning and the brain-age paradigm to assess whether FD patients' brains appear older than normal and to validate brain-predicted age difference (brain-PAD) as a possible disease severity biomarker. MRI scans of FD patients and healthy controls (HCs) from a single Institution were, retrospectively, studied. The Fabry stabilization index (FASTEX) was recorded as a measure of disease severity. Using minimally preprocessed 3D T1-weighted brain scans of healthy subjects from eight publicly available sources (N = 2160; mean age = 33 years [range 4-86]), we trained a model predicting chronological age based on a DenseNet architecture and used it to generate brain-age predictions in the internal cohort. Within a linear modeling framework, brain-PAD was tested for age/sex-adjusted associations with diagnostic group (FD vs. HC), FASTEX score, and both global and voxel-level neuroimaging measures. We studied 52 FD patients (40.6 ± 12.6 years; 28F) and 58 HC (38.4 ± 13.4 years; 28F). The brain-age model achieved accurate out-of-sample performance (mean absolute error = 4.01 years, R2 = .90). FD patients had significantly higher brain-PAD than HC (estimated marginal means: 3.1 vs. -0.1, p = .01). Brain-PAD was associated with FASTEX score (B = 0.10, p = .02), brain parenchymal fraction (B = -153.50, p = .001), white matter hyperintensities load (B = 0.85, p = .01), and tissue volume reduction throughout the brain. We demonstrated that FD patients' brains appear older than normal. Brain-PAD correlates with FD-related multi-organ damage and is influenced by both global brain volume and white matter hyperintensities, offering a comprehensive biomarker of (neurological) disease severity.

Abstract 6696: Microbial signatures and serum markers in colon cancer of African American patients

Abstract Among all the racial/ethnic groups, African American (AA) patients have the highest incidence of CRC and mortality rate. There is growing evidence indicating that the oral bacteria might translocate to the intestine, potentially causing disruptions in the balance of gut microbes. Our study delves into the complex interplay between oral pathogens, gut microbiota, and colon carcinogenesis in AA patients. Methods: 16S rRNA sequencing of tumor and non-tumor tissues, utilized qPCR for detection of oral bacteria Fusobacterium nucleatum (Fn) and Porphyromonas gingivalis (Pg) relative abundance, performed cytokine profiling via multiplex ELISA, and employed NAPPA for antibody response assessment. Results: Colon tumor tissues had lower microbial diversity, notably in right-sided tumors, with distinct biofilm-associated bacteria. Novel discoveries emerged from differential abundance testing, revealing Prevotella intermedia and Treponema socranski to be associated with early cancer stage and left-sided location, and Fusobacterium necrophorum with advanced cancer stage and right-sided location. qPCR demonstrated Fn and Pg elevation in right-sided tumors and late cancer stages. Both were detected in 45% of tumors versus 37% in non-tumor tissues and 19.15% of tumors and 25.53% in non-tumor tissues, respectively. Fn-positive groups exhibited distinct microbial signatures, with altered bacterial abundances and dysbiosis, including increased CRC-associated bacteria Faecalibacterium and Helicobacter, increased oral pathogen abundance (Fusobacterium, Porphyromonas, Prevotella, Treponema), and reduced beneficial bacteria. Serological analysis highlighted elevated levels of IL-2, IL-10, IFN-γ, and RANK in advanced cancer stages and increased CRP levels in right-sided tumors. By NAPPA analysis, 30 bacterial proteins (anti-IgG) showed a seroprevalence of more than 15% in the samples, with those being the most seroprevalent anti-HP131 and anti-HP-1564 (68% and 61% of all samples) of Helicobacter pylori, and anti-msnK (64%) of Streptococcus gallolyticus. Conclusions: Our study emphasized the reduced diversity in tumor tissues, particularly in right-sided tumors in AA colon cancer. Fn presence in colonic tumors correlated with CRC-associated bacteria and oral pathogen aggregation, suggesting its potential role in cancer pathogenesis. Combining the analysis of cytokines and pathogenic bacteria antibodies may serve as broader serological biomarkers for disease severity and location. These findings advance our comprehension of microbiota-cancer interactions, directing personalized diagnostics and treatments in this population. Citation Format: Sofia Carolina Tortora, Emily Vogtmann, Laura Martello-Rooney. Microbial signatures and serum markers in colon cancer of African American patients [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 6696.

Blood sphingolipid as a novel biomarker in patients with neuromyelitis optica spectrum disorder

BackgroundSphingolipids are signaling molecules and structural components of the axolemma and myelin sheath. Plasma sphingolipid levels may reflect disease status of neuromyelitis optica spectrum disorder (NMOSD). We aimed to examine plasma sphingolipids as disease severity biomarkers for NMOSD and compare their characteristics with those of serum neurofilament light chain (sNfL) and glial fibrillary acidic protein (sGFAP). MethodsWe measured plasma sphingolipids, sNfL, and sGFAP levels in NMOSD cases with anti-aquaporin-4-antibody. An unbiased approach, partial least square discriminant analysis (PLS-DA), was utilized to determine whether sphingolipid profiles differ according to the disease state of NMOSD (presence, moderate-to-severe disability [Expanded Disease Severity Scale, (EDSS) > 3.0], and relapses). ResultsWe investigated 81 patients and 10 controls. PLS-DA models utilizing sphingolipids successfully differentiated patients with EDSS > 3.0, but failed to identify the presence of disease and relapses. Ceramide-C14—a significant contributor to differentiating EDSS > 3.0—positively correlated with EDSS, while its levels were independent of age and the presence of relapses. This characteristic was unique from those of sNfL and sGFAP, which were affected by age and relapses as well as EDSS. ConclusionPlasma sphingolipids may be useful NMOSD biomarkers for disability with distinct characteristics compared to sNfL and sGFAP.

Predictive Value of RDW/PLT for Progression of COVID-19 Pneumonia: A Potential Biomarker for Disease Severity

Identifying reliable predictors for COVID-19 pneumonia progression is crucial for effective patient management. The purpose of this study is to evaluate the Red Cell Distribution Width to Platelet Ratio (RDW/PLT) as a potential predictive biomarker for the development of moderate to severe COVID-19 pneumonia. Conducting a retrospective analysis from August 2021 to March 2023, we categorized patients with moderate COVID-19 pneumonia at admission into different severity groups. The objective was to explore clinical and laboratory variables associated with disease progression. Fifty-three patients initially diagnosed with moderate COVID-19 were studied, of which 17 progressed to severe disease. Univariate logistic regression analyzed various factors, including age, PLT, RDW-SD, RDW/PLT, AST, ALB, CRP, and IL-6, evaluating their correlation (P &lt; 0.05) with higher odds ratios of a poor prognosis. To ascertain these factors’ predictive power, Receiver Operating Characteristic (ROC) curve analysis was used. Univariate logistic regression highlighted several factors associated with increased odds ratios for poor prognosis. Notably, RDW/PLT exhibited the highest predictive value (AUC: 0.925, 95% CI 0.858–0.991) among single parameters in predicting the risk of COVID-19 progression. This study underscores the potential of RDW/PLT as an accessible and cost-effective biomarker for determining COVID-19 pneumonia severity. The findings support its utility in risk stratification and clinical decision-making, offering valuable insights for effective patient management strategies.

Shotgun metagenomics and systemic targeted metabolomics highlight indole-3-propionic acid as a protective gut microbial metabolite against influenza infection

ABSTRACT The gut-to-lung axis is critical during respiratory infections, including influenza A virus (IAV) infection. In the present study, we used high-resolution shotgun metagenomics and targeted metabolomic analysis to characterize influenza-associated changes in the composition and metabolism of the mouse gut microbiota. We observed several taxonomic-level changes on day (D)7 post-infection, including a marked reduction in the abundance of members of the Lactobacillaceae and Bifidobacteriaceae families, and an increase in the abundance of Akkermansia muciniphila. On D14, perturbation persisted in some species. Functional scale analysis of metagenomic data revealed transient changes in several metabolic pathways, particularly those leading to the production of short-chain fatty acids (SCFAs), polyamines, and tryptophan metabolites. Quantitative targeted metabolomics analysis of the serum revealed changes in specific classes of gut microbiota metabolites, including SCFAs, trimethylamine, polyamines, and indole-containing tryptophan metabolites. A marked decrease in indole-3-propionic acid (IPA) blood level was observed on D7. Changes in microbiota-associated metabolites correlated with changes in taxon abundance and disease marker levels. In particular, IPA was positively correlated with some Lactobacillaceae and Bifidobacteriaceae species (Limosilactobacillus reuteri, Lactobacillus animalis) and negatively correlated with Bacteroidales bacterium M7, viral load, and inflammation markers. IPA supplementation in diseased animals reduced viral load and lowered local (lung) and systemic inflammation. Treatment of mice with antibiotics targeting IPA-producing bacteria before infection enhanced viral load and lung inflammation, an effect inhibited by IPA supplementation. The results of this integrated metagenomic-metabolomic analysis highlighted IPA as an important contributor to influenza outcomes and a potential biomarker of disease severity.

Quantitative whole-body muscle MRI in idiopathic inflammatory myopathies including polymyositis with mitochondrial pathology: indications for a disease spectrum.

Inflammatory myopathies (IIM) include dermatomyositis (DM), sporadic inclusion body myositis (sIBM), immune-mediated necrotizing myopathy (IMNM), and overlap myositis (OLM)/antisynthetase syndrome (ASyS). There is also a rare variant termed polymyositis with mitochondrial pathology (PM-Mito), which is considered a sIBM precursor. There is no information regarding muscle MRI for this rare entity. The aim of this study was to compare MRI findings in IIM, including PM-Mito. This retrospective analysis included 41 patients (7 PM-Mito, 11 sIBM, 11 PM/ASyS/OLM, 12 IMNM) and 20 healthy controls. Pattern of muscle involvement was assessed by semiquantitative evaluation, while Dixon method was used to quantify muscular fat fraction. The sIBM typical pattern affecting the lower extremities was not found in the majority of PM-Mito-patients. Intramuscular edema in sIBM and PM-Mito was limited to the lower extremities, whereas IMNM and PM/ASyS/OLM showed additional edema in the trunk. Quantitative assessment showed increased fat content in sIBM, with an intramuscular proximo-distal gradient. Similar changes were also found in a few PM-Mito- and PM/ASyS/OLM patients. In sIBM and PM-Mito, mean fat fraction of several muscles correlated with clinical involvement. As MRI findings in patients with PM-Mito relevantly differed from sIBM, the attribution of PM-Mito as sIBM precursor should be critically discussed. Some patients in PM/ASyS/OLM and PM-Mito group showed MR-morphologic features predominantly observed in sIBM, indicative of a spectrum from PM/ASyS/OLM toward sIBM. In some IIM subtypes, MRI may serve as a biomarker of disease severity.