Effects of a medium cut-off dialyzer on inflammation and cardiac and vascular function in hemodialysis patients with heart failure.

INTRODUCTION: Expanded hemodialysis (HDx) could provide clearance of larger middle-molecule uremic toxins. We compared the effect of hemodialysis with medium cut-off membranes and high-flux (HFHD) membranes regarding changes in inflammation and vascular and left ventricular function. METHODS: This was a single-center, prospective, parallel-group comparative study. Patients were divided into two groups (HDx: 25 patients and HFHD: 26 patients). All measurements were performed at baseline and 12 weeks. Serum c-reactive protein, interkelukin-18, pentraxin-3, ß-2 microglobulin, and brain natriuretic peptide were measured. We used pulse wave velocity and augmentation index to assess arterial stiffness and echocardiography to evaluate left and right ventricular function. FINDINGS: We enrolled 51 patients. Although serum c-reactive protein, interkelukin-18, pentraxin 3, and ß-2 microglobulin were significantly decreased in the HDx group (p = 0.02, p < 0.001, p = 0.002, and p = 0.02, respectively), there was no significant change in HFHD group at 12th week. Serum c-reactive protein and interkelukin-18were significantly lower in the HDx group compared to the HFHD group in the 12th week (p = 0.007 and p = 0.03, respectively). We observed a significant decrease in pulse wave velocity in the HDx group at the end of the study (p = 0.03). Although there was no significant change in pulse wave velocity in the HFHD group, pulse wave velocity was similar between the HDx and HFHD groups in the 12th week. We detected a significant decrease in the mean isovolumetric relaxation time in the HDx group (p = 0.006). However, there was no significant difference in isovolumetric relaxation time between the HDx and HFHD groups in the 12th week. DISCUSSION: HDx provides better clearance of middle molecular uremic toxins and inflammatory biomarkers, and it may be associated with better central hemodynamic parameters and diastolic functions.

Longitudinal soluble marker profiles reveal strong association between cytokine storms resulting from macrophage activation and disease severity in COVID-19 disease.

SARS-CoV2 infection results in a range of disease severities, but the underlying differential pathogenesis is still not completely understood. At presentation it remains difficult to estimate and predict severity, in particular, identify individuals at greatest risk of progression towards the most severe disease-states. Here we used advanced models with circulating serum analytes as variables in combination with daily assessment of disease severity using the SCODA-score, not only at single time points but also during the course of disease, to correlate analyte levels and disease severity. We identified a remarkably strong pro-inflammatory cytokine/chemokine profile with high levels for sCD163, CCL20, HGF, CHintinase3like1 and Pentraxin3 in serum which correlated with COVID-19 disease severity and overall outcome. Although precise analyte levels differed, resulting biomarker profiles were highly similar at early and late disease stages, and even during convalescence similar biomarkers were elevated and further included CXCL3, CXCL6 and Osteopontin. Taken together, strong pro-inflammatory marker profiles were identified in patients with COVID-19 disease which correlated with overall outcome and disease severity.

Influence of Dulaglutide on Serum Biomarkers of Atherosclerotic Plaque Instability: An Interventional Analysis of Cytokine Profiles in Diabetic Subjects-A Pilot Study.

Background and Objectives: The rise in global diabetes cases, reaching a staggering 529 million in 2021 from 108 million in 1980, underscores the urgency of addressing its complications, notably macrovascular ones like coronary artery, cerebrovascular, and peripheral artery diseases, which contribute to over 50% of diabetes mortality. Atherosclerosis, linked to hyperglycemia-induced endothelial dysfunction, is pivotal in cardiovascular disease development. Cytokines, including pentraxin 3 (PTX3), copeptin, lipoprotein(a) [Lp(a)], and matrix metalloproteinase-9 (MMP-9), influence atherosclerosis progression and plaque vulnerability. Inhibiting atherosclerosis progression is crucial, especially in diabetic individuals. Glucagon-like peptide 1 receptor agonists (GLP-1 RAs), increasingly used for type 2 diabetes, show promise in reducing the cardiovascular risk, sparking interest in their effects on atherogenesis. This study sought to examine the effects of glucagon-like peptide-1 receptor agonists (GLP-1 RAs) on biomarkers that indicate the instability of atherosclerotic plaques. These biomarkers include pentraxin 3 (PTX3), copeptin (CPC), matrix metalloproteinase-9 (MMP-9), and lipoprotein(a) [Lp(a)]. Materials and Methods: A total of 34 participants, ranging in age from 41 to 81 years (with an average age of 61), who had been diagnosed with type 2 diabetes mellitus (with a median HbA1c level of 8.8%), dyslipidemia, and verified atherosclerosis using B-mode ultrasonography, were included in the study. All subjects were eligible to initiate treatment with a GLP-1 RA-dulaglutide. Results: Significant reductions in anthropometric parameters, blood pressure, fasting glucose levels, and HbA1c levels were observed posttreatment. Moreover, a notable decrease in biochemical markers associated with atherosclerotic plaque instability, particularly PTX3 and MMP-9 (p < 0.001), as well as Lp(a) (p < 0.05), was evident following the GLP-1 RA intervention. Conclusions: These findings underscore the potential of GLP-1 RAs in mitigating atherosclerosis progression and plaque vulnerability, thus enhancing cardiovascular outcomes in individuals with type 2 diabetes mellitus.

The impact of obesity, age, and gender on plasmatic levels of selected glycoprotein biomarkers and miRNA-499 in OSA patients.

BACKGROUND: The current obstructive sleep apnea (OSA) diagnostic uses polysomnography or limited polygraphy and requires specialized personnel and technical equipment. Glycoprotein biomarkers and microRNAs are being explored as a possible new method for screening. We aimed to evaluate whether certain biomarkers and microRNA, previously identified as related to OSA, could be influenced by factors such as gender, age, and obesity level in patients with OSA. METHODS: In this retrospective analytical study, patients with moderate to severe OSA (n = 130) were compared with the control group. Serum levels of selected biomarkers and microRNA were taken from both groups. The group of OSA patients was then stratified by gender, obesity level, and age to see the possible influence of those variables on biomarker levels. RESULTS: Levels of all studied biomarkers - C-reactive protein (CRP), high-sensitivity troponin I (hsTnI), pentraxin-3 (PTX-3), and microRNA-499 were significantly higher in patients with OSA compared to the control group. In the OSA group only hsTnI showed a statistically significant relationship with gender. Levels of CRP and hsTnI showed a significant dependence on the level of obesity. Dependency on age was proven for hsTnI. CRP, PTX-3, and microRNA-499 did not have any statistically significant relationship with age. CONCLUSION: We found that serum levels of pentraxin-3 and microRNA-499 in patients with moderate to severe obstructive sleep apnoea are independent of gender, obesity, and age. CRP was affected by the level of obesity and hsTnI was influenced by all 3 variables. We consider these findings important for further research of OSA biomarkers.

Plasma pentraxin-3 levels and its role in childhood obesity-Is it anti-inflammatory? A matched group study.

OBJECTIVE: Obesity has been associated with chronic low-grade systemic inflammation. This study aimed to investigate the relationship of pentraxin-3 (PTX-3) with anthropometric measurements, dietary content and physical activity level in children. DESIGN: A matched group study. PATIENTS: This study was conducted with 91 children aged 6-17 years, divided into two groups: "non-obese group" (Body Mass Index Standard Deviation Score [BMI SDS] <95th percentile) and "obese group" (BMI SDS ≥95th percentile). MEASUREMENTS: Plasma PTX-3 levels. RESULTS: The mean age of 91 children included in the study was 12.34 ± 2.86 years. Plasma PTX-3 levels were significantly higher in obese children (p = .028). No significant correlation was found between BMI SDS and plasma PTX-3 values, but a weak positive correlation was found when physical activity level was controlled (r = .176, p = .049). In addition, it was found that fat mass was a partial mediator of plasma PTX-3 level, and an increase in the amount of subcutaneous adipose tissue negatively affected plasma PTX-3 level. Plasma PTX-3 level showed a weak positive correlation (r = .223, p = .017) with physical activity score and dietary polyunsaturated fatty acid intake, while a weak negative correlation with neutrophil-to-lymphocyte ratio. One unit increase in physical activity score or polyunsaturated fatty acid level caused 0.730 and 2.061 unit increases in plasma PTX-3 level, respectively; while one unit increase in dietary fat intake caused 0.413-unit decrease. CONCLUSION: There was an indirect relationship between the amount of subcutaneous adipose tissue and PTX-3 level. The results of our study suggested that plasma PTX-3 was associated with lower levels of inflammation in children.

A study of inflammatory biomarkers in crystalline silica exposed rock drillers.

BACKGROUND: Crystalline silica (CS) exposure can cause serious lung disease in humans, but mechanisms of pulmonary toxicity have not been completely elucidated. AIMS: To assess pro-inflammatory and anti-inflammatory biomarkers and biomarkers related to the development of chronic obstructive pulmonary disease and fibrosis in serum of rock drillers exposed to CS. METHODS: Rock drillers (N = 123) exposed to CS and non-specified particulate matter (PM) were compared to 48 referents without current or past exposure to PM in a cross-sectional study. RESULTS: The rock drillers had been exposed to CS for 10.7 years on average. Geometric mean (GM) current exposure was estimated to 36 µg/m3. Their GM concentration of matrix metalloproteinase 12 (MMP-12) was significantly higher (16 vs. 13 ng/L; p = 0.04), while interleukin (IL) 6 and IL-8 were significantly lower compared to the referents. Also pentraxin 3 was significantly lower (3558 vs. 4592 ng/L; p = 0.01) in the rock drillers. A dose-response relationship was observed between cumulative exposure to CS and MMP-12, the highest exposed subgroup having significantly higher MMP-12 concentrations than the referents. CONCLUSION: Exposure to CS may increase circulating MMP-12 concentrations in a dose-response related fashion. The results may also suggest a down-regulation of pro-inflammatory pathways.

Post-COVID Trajectory of Pentraxin 3 Plasma Levels Over 6 Months and Their Association with the Risk of Developing Post-Acute Depression and Anxiety.

BACKGROUND AND OBJECTIVES: Clinical manifestations of coronavirus disease 2019 (COVID-19) often persist after acute disease resolution. Underlying molecular mechanisms are unclear. The objective of this original article was to longitudinally measure plasma levels of markers of the innate immune response to investigate whether they associate with and predict post-COVID symptomatology. METHODS: Adult patients with previous severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection during the first pandemic wave who underwent the 6-month multidisciplinary follow-up were included. Plasma levels of pentraxin 3 (PTX3), the complement components C3a and C5a, and chitinase-3 like-protein-1 (CHI3L1) were measured at hospital admission during acute disease (baseline) and at 1 and 6 months after hospital discharge. Associations with post-COVID-19 sequelae at 6 months were investigated using descriptive statistic and multiple regression models. RESULTS: Ninety-four COVID-19 patients were included. Baseline PTX3, C5a, C3a, and CHI3L1 did not predict post-COVID-19 sequelae. The extent of the reduction of PTX3 over time (delta PTX3) was associated with lower depressive and anxiety symptoms at 6 months (both p < 0.05). When entering sex, age, need for intensive care unit or non-invasive ventilation during hospital stay, psychiatric history, and baseline PTX3 as nuisance covariates into a generalized linear model (GLM), the difference between baseline and 6-month PTX3 levels (delta PTX3) significantly predicted depression (χ2 = 4.66, p = 0.031) and anxiety (χ2 = 4.68, p = 0.031) at 6 months. No differences in PTX3 levels or PTX3 delta were found in patients with or without persistent or new-onset other COVID-19 symptoms or signs at 6 months. Plasma levels of C3a, C5a, and CHI3L1 did not correlate with PTX3 levels at either time point and failed to associate with residual or de novo respiratory or systemic clinical manifestations of the disease at 6 months. CONCLUSIONS: A lower reduction of plasma PTX3 after acute COVID-19 associates with the presence of depression and anxiety, suggesting an involvement of inflammation in post-COVID-19 psychopathology and a potential role of PTX3 as a biomarker.

Predictive potential of various plasma inflammation-, angiogenesis-, and extracellular matrix remodeling-associated mediators for intra-amniotic inflammation and/or microbial invasion of the amniotic cavity in preterm labor.

PURPOSE: To determine whether various inflammatory-, angiogenic/anti-angiogenic-, and extracellular matrix remodeling-associated proteins in plasma, alone or in combination with conventional blood-based markers, can predict intra-amniotic inflammation and/or microbial invasion of the amniotic cavity (IAI/MIAC) in women with spontaneous preterm labor (PTL). METHODS: A total of 193 singleton pregnant women with PTL (23-33 weeks) were included in this retrospective cohort study. Plasma samples were obtained at the time of amniocentesis. Amniotic fluid (AF) was cultured for microorganism detection and consequent MIAC diagnosis. IL-6 levels were determined in AF and used to identify IAI (AF IL-6 ≥ 2.6 ng/mL). Endostatin, haptoglobin, IGFBP-2/3, LBP, M-CSF, MMP-2/8, pentraxin 3, PlGF, S100A8/A9, and VEGFR-1 levels were assayed in plasma samples by ELISA. CRP levels and neutrophil-to-lymphocyte ratio (NLR) were measured. RESULTS: Plasma LBP, MMP-8, and S100A8/A9 levels, CRP levels, and NLR were significantly higher, and plasma IGFBP-2 and MMP-2 levels were significantly lower in women with IAI/MIAC than in those without this condition, whereas no baseline variables differed significantly between the two groups. Using a stepwise regression analysis, a noninvasive prediction model for IAI/MIAC was developed, which included plasma LBP, MMP-2, and MMP-8 levels (area under the curve [AUC], 0.785). The AUC for this prediction model was significantly or borderline greater than that of any single factor included in the model. CONCLUSIONS: IGFBP-2, LBP, MMP-2, MMP-8, and S100A8/A9 may represent valuable plasma biomarkers for predicting IAI/MIAC in women with PTL. Combination of LBP, MMP-2, and MMP-8 expression data can significantly improve the predictive potential for IAI/MIAC.

Pentraxin 3 in Circulating Microvesicles: a Potential Biomarker for Acute Heart Failure After Cardiac Surgery with Cardiopulmonary Bypass.

The aim of this study was to investigate whether pentraxin 3 (PTX3) in microvesicles (MVs) can be a valuable biomarker for the prediction of acute heart failure (AHF) after cardiac surgery with cardiopulmonary bypass (CPB). One hundred and twenty-four patients undergoing cardiac surgery with CPB were included and analyzed (29 with AHF and 95 without AHF). The concentrations of PTX3 in MVs isolated from plasma were measured by ELISA kits before, 12 h, and 3 days after surgery. Patients' demographics, medical history, surgical data, and laboratory results were collected. The levels of PTX3 in MVs were significantly elevated during perioperative surgery, which was increased more in the AHF group. The concentrations of PTX3 in MVs at postoperative 12 h were independent risk factors for AHF with the area under the ROC curve of 0.920. The concentration of PTX3 in MVs may be a novel biomarker for prediction of AHF after cardiac surgery.

Can calcitonin gene-related peptide (CGRP) and pentraxin-3 (PTX-3) be useful in diagnosing acute migraine attack?

PURPOSE: Even if migraine is not fatal, it is a common and challenging disease with adverse effects on individuals' lives. The lack of objective diagnostic tools causes delays in diagnosis and treatment initiation. The primary aim of this study is to reveal the diagnostic value of Calcitonin Gene-Related Peptide (CGRP) and Pentraxin-3 (PTX-3) in acute migraine. To this aim, we compared the serum CGRP and PTX-3 levels of migraine patients with acute attacks to those in healthy individuals. MATERIAL AND METHOD: A total of 135 individuals (85 patients with migraine attacks with or without aura and 50 healthy controls) participated in the study. Serum CGRP and PTX-3 levels were measured with ELISA analysis. A p value less than 0.05 was considered significant. RESULTS: Serum CGRP [146.70 (21.52-413.67) vs. 65.90 (3.80-256.60) pg/mL] and PTX-3 levels [12.71 (0.62-33.97) vs. 1.01 (0.06-9.48) ng/mL] were higher in patients with migraine attack than the control group (p < 0.01 and p < 0.01, respectively). ROC analysis showed that the cutoff value for serum CGRP was 121.39 pg/mL (AUC: 0.751, Sen:%61, Spe:%64) whereas the cutoff value for PTX-3 was 4,06 ng/mL (AUC:0.876, Sen:%73, Spe:%76). Serum CGRP levels were positively correlated with pain intensity. Serum CGRP and PTX-3 levels did not differ across gender groups and presence of aura in subgroup analysis. CONCLUSION: Patients with acute migraine attacks have higher serum CGRP and PTX-3 levels than controls. Both biomarkers show high potential for the diagnosis of a migraine attack.

An observational, non-interventional study for the follow-up of patients with amyloidosis who received miridesap followed by dezamizumab in a phase 1 study.

BACKGROUND: Miridesap depletes circulating serum amyloid P (SAP) and dezamizumab (anti-SAP monoclonal antibody) targets SAP on amyloid deposits, triggering amyloid removal. In a phase 1, first-in-human study (FIHS), progressive amyloid removal was observed in some patients after ≤ 3 cycles of miridesap/dezamizumab. METHODS: This observational, non-interventional study in patients who received miridesap/dezamizumab during the FIHS (planned follow-up: 5 years) evaluated response to treatment based on routine assessments of disease status and key organ function. In a post hoc analysis, patients responding to treatment in the FIHS during follow-up were identified as responders and further categorized as sustained or declining responders. RESULTS: In the FIHS, 17/23 patients were treatment responders. Of these patients, seven (immunoglobulin light chain [AL], n = 6; serum amyloid A, n = 1) were considered sustained responders and ten (fibrinogen-a alpha chain [AFib], n = 5; AL, n = 4; apolipoprotein A-I, n = 1) were considered declining responders. We primarily present responder patient-level data for functional, cardiac, laboratory and imaging assessments conducted during the follow-up period, with non-responder data presented as supplementary. CONCLUSION: No further development of miridesap/dezamizumab is planned in amyloidosis. However, long-term follow-up of these patients may provide insight into whether active removal of amyloid deposits has an impact on disease progression. TRIAL REGISTRATION: ClinicalTrials.gov, NCT01777243. Registered 28 January 2013, https://clinicaltrials.gov/ct2/show/study/NCT01777243 .

Pentraxin-3 as a predictive marker of mortality in sepsis: an updated systematic review and meta-analysis.

BACKGROUND: The purpose of this study was to clarify the prognostic value of Pentraxin-3 (PTX3) on the mortality of patients with sepsis. METHODS: Publications published up to January 2021 were retrieved from PubMed, EMBASE, and the Cochrane library. Data from eligible cohort and case-control studies were extracted for the meta-analysis. Multivariate regression analysis was used to evaluate the correlation of the outcomes with sample size and male proportion. RESULTS: A total of 17 studies covering 3658 sepsis patients were included. PTX3 level was significantly higher in non-survivor compared to survivor patients (SMD (95% CI): -1.06 (-1.43, -0.69), P < 0.001). Increased PTX3 level was significantly associated with mortality (HR (95% CI): 2.09 (1.55, 2.81), P < 0.001). PTX3 showed good predictive capability for mortality (AUC:ES (95% CI): 0.73 (0.70, 0.77), P < 0.001). The outcome comparing PTX3 level in non-survivors vs. survivors and the outcome of the association between PTX3 and mortality were associated with sample size but not male proportion. AUC was associated with both sample size and male proportion. CONCLUSIONS: PTX3 level was significantly higher in non-survivor compared to survivor patients with sepsis. Elevated PTX3 level was significantly associated with mortality. Furthermore, the level of PTX3 might predict patient mortality.

Increased Circulating Pentraxin 3 Levels in Patients with Rheumatoid Arthritis: A Meta-analysis.

BACKGROUND: Pentraxin 3 (PTX3), a soluble pattern recognition molecule, not only acts as a promising indicator reflecting the disease activity of rheumatoid arthritis (RA) patients but exerts essential pathogenic roles in the progression of RA and serves as a potential therapeutic target for RA patients. Our study intends to systematically evaluate the circulating PTX3 levels and their potential influencing factors in RA patients. METHODS: Articles regarding the circulating PTX3 levels of RA patients were identified in Pubmed, Embase, China National Knowledge Infrastructure (CNKI), and Cochrane databases. Standardized mean difference (SMD) and corresponding 95% confidence intervals (95% CI) were calculated and further illustrated by the forest plot. Egger's regression test and sensitivity analysis were conducted to assess the publication bias and stability of the results, respectively. RESULTS: Twenty articles with 21 individual studies were recruited in our meta-analysis. The overall results revealed that compared to healthy controls, RA patients had significantly higher circulating PTX3 levels (pooled SMD = 0.97, 95% CI: 0.48 to 1.45). Subgroup analyses further demonstrated that compared to healthy controls, RA patients of age ≤ 50 years, 2.6 < disease activity score in 28 joints (DAS28) ≤ 3.2, 3.2 < DAS28 ≤ 5.1, DAS28 > 5.1, C-reactive protein (CRP) levels > 10 mg/L, erythrocyte sedimentation rate (ESR) > 20 mm/h, and disease duration > 5 years had significantly higher circulating PTX3 levels, respectively; whereas RA patients of age > 50 years, DAS28 ≤ 2.6, CRP levels ≤ 10 mg/L, ESR ≤ 20 mm/h and disease duration ≤ 5 years had no significantly altered circulating PTX3 levels, respectively. Additionally, no matter whether the patients were of Caucasian ethnicity or not, circulating PTX3 levels were significantly increased in RA patients. CONCLUSION: Compared to healthy controls, circulating PTX3 levels are significantly increased in RA patients, which are influenced by age, disease activity, CRP levels, ESR, and disease duration.

The effect of TNF-α inhibitor treatment on microRNAs and endothelial function in collagen induced arthritis.

Chronic inflammation causes dysregulated expression of microRNAs. Aberrant microRNA expression is associated with endothelial dysfunction. In this study we determined whether TNF-α inhibition impacted the expression of miRNA-146a-5p and miRNA-155-5p, and whether changes in the expression of these miRNAs were related to inflammation-induced changes in endothelial function in collagen-induced arthritis (CIA). Sixty-four Sprague-Dawley rats were divided into control (n = 24), CIA (n = 24) and CIA+etanercept (n = 16) groups. CIA and CIA+etanercept groups were immunized with bovine type-II collagen, emulsified in incomplete Freund's adjuvant. Upon signs of arthritis, the CIA+etanercept group received 10mg/kg of etanercept intraperitoneally, every three days. After six weeks of treatment, mesenteric artery vascular reactivity was assessed using wire-myography. Serum concentrations of TNF-α, C-reactive protein, interleukin-6, vascular adhesion molecule-1 (VCAM-1) and pentraxin-3 (PTX-3) were measured by ELISA. Relative expression of circulating miRNA-146a-5p and miRNA-155-5p were determined using RT-qPCR. Compared to controls, circulating miRNA-155-5p, VCAM-1 and PTX-3 concentrations were increased, and vessel relaxation was impaired in the CIA (all p<0.05), but not in the CIA+etanercept (all p<0.05) groups. The CIA group had greater miRNA-146a-5p expression compared to the CIA+etanercept group (p = 0.005). Independent of blood pressure, miRNA-146a-5p expression was associated with increased PTX-3 concentrations (p = 0.03), while miRNA-155-5p expression was associated with impaired vessel relaxation (p = 0.01). In conclusion, blocking circulating TNF-α impacted systemic inflammation-induced increased expression of miRNA-146a-5p and miRNA-155-5p, which were associated with endothelial inflammation and impaired endothelial dependent vasorelaxation, respectively.

Serum amyloid P component level is associated with clinical response to escitalopram treatment in patients with major depressive disorder.

Serum amyloid P component (SAP) is a universal constituent of human amyloid deposits, which has been implicated in Alzheimer's disease and major depressive disorder (MDD). However, the relationship between SAP level and depression severity remains obscure. The aims of this study were to investigate how SAP is involved in depression and to explore the association between SAP level and antidepressant treatment response. Patients with MDD (n = 85) who received escitalopram monotherapy for 8-12 weeks were selected from a multicenter open-label randomized clinical trial. The same number of healthy controls was recruited. Depression severity was measured according to the Hamilton Depression Rating Scale (HAMD-17) at baseline and weeks 4, 8, and 12. The plasma levels of SAP were measured at baseline, week 2 and week 12. As a result, baseline levels of SAP were significantly higher in depressed patients than in control subjects (p < 0.001). SAP levels at baseline were negatively associated with depression severity after escitalopram treatment (p < 0.05), and the changes in SAP levels from baseline to week 12 were highly correlated with the severity of depressive symptoms based on the HAMD-17 score (p < 0.05). Interestingly, treatment with escitalopram significantly decreased the plasma levels of SAP in females, but not in males. Altogether, our results suggest that SAP not only involved in the pathobiology of depression but also mediates the action of antidepressant medications.

Prediction of Respiratory Failure and Mortality in COVID-19 Patients Using Long Pentraxin PTX3.

The course of COVID-19 is unpredictable, ranging from asymptomatic to respiratory failure and death. Prognostic biomarkers are urgently needed. We hypothesized that long pentraxin PTX3 could be a valuable plasma biomarker due to its essential role in inflammatory processes. In a prospective hospitalized COVID-19 derivation cohort (n = 126) during the spring of 2020, we measured PTX3 within 4 days of admission. The predictive value of mechanical ventilation (MV) and 30-day mortality compared with clinical parameters and other markers of inflammation were assessed by logistic regression analysis and expressed as odds ratio (OR) with 95% confidence interval (CI). Analyses were repeated in a prospective validation cohort (n = 112) of hospitalized patients with COVID-19 treated with remdesivir and dexamethasone. Thirty-day mortality in the derivation cohort was 26.2%. In patients who died, the median PTX3 concentration upon admission was 19.5 ng/mL (IQR: 12.5-33.3) versus 6.6 ng/mL (IQR 2.9-12.3) (p < 0.0001) for survivors. After adjustment for covariates, the odds of 30-day mortality increased two-fold for each doubling of PTX3 (OR 2.03 [95% CI: 1.23-3.34], p = 0.006), which was also observed in the validation cohort (OR 1.70 [95% CI: 1.09-2.67], p = 0.02). Similarly, PTX3 levels were associated with MV. After adjustment for covariates, OR of MV was 2.34 (95% CI: 1.33-4.12, p = 0.003) in the derivation cohort and 1.64 (95% CI: 1.03-2.62, p = 0.04) in the validation cohort. PTX3 appears to be a useful clinical biomarker to predict 30-day respiratory failure and mortality risk in COVID-19 patients treated with and without remdesivir and dexamethasone.

Analyses of interleukin-6, presepsin and pentraxin-3 in the diagnosis and severity of late-onset preeclampsia.

INTRODUCTION: The etiology/pathophysiology of preeclampsia remains an enigma. Maternal inflammation (humoral and cellular) is a key factor in the etiology of late-onset preeclampsia (L-PrE). Presepsin is split out from the phagocytes membranes after phagocytosis. It is known as a novel inflammation marker. To our knowledge, this is the first study in literature in English to investigate maternal blood concentrations of presepsin in preeclampsia and healthy pregnant women. METHODS: We examined maternal plasma interleukin-6, presepsin and pentraxin-3 concentrations in pregnant women with (n = 44) and without L-PrE (n = 44). These three inflammatory markers concentrations measured using enzyme-linked immunosorbent assays were compared. RESULTS: The mean maternal age and gestational age at sampling are similar in the both groups (p ≥ .05). Interleukin-6, presepsin and pentraxin-3 concentrations differed between the groups (p < .05). There was no difference between the three inflammatory markers concentrations in patients with mild (22 patients) and severe (22 patients) preeclampsia in L-PrE (p ≥ .05). A significant discriminative role of interleukin-6, presepsin and pentraxin-3 for presence of L-PrE, with cutoff values of 39.74 pg/mL, 309.88 mg/L and 34.96 ng/mL, respectively, were reported in a ROC curve analysis. When the patients with and without small for gestational age infants (12 patients and 76 patients, respectively) were compared, it was determined that there was no differences between the interleukin-6, but there were differences between the presepsin and pentraxin-3 concentrations (p = .016, p = .008, respectively). CONCLUSION: Lower concentrations of interleukin-6/presepsin and higher concentrations of pentraxin-3 were associated with the development of preeclampsia. Further investigations of inflammatory/immunity markers in pregnancy are required and may ultimately lead to novel therapeutic approaches to treat complications of pregnancy.

Pentraxin 3 concentration is associated with poor outcomes in patients with coronary artery disease: a systematic review and dose-response meta-analysis.

BACKGROUND: The amount of plasma pentraxin 3 (PTX3) is gradually being considered as a novel biomarker in forecasting poor clinical outcomes in patients with coronary artery disease (CAD). However, very little is known about the connection between PTX3 and CAD. This dose-response meta-analysis was carried out to quantify the relationship between circulating PTX3 concentration and CAD prognosis. METHODS: A systematic literature search was conducted using PubMed, EuropePMC, ProQuest, EBSCOhost, SCOPUS, Cochrane Library, and Google Scholar up until April 2021. The primary outcome of this study consisted of mortality and major adverse cardiovascular events (MACEs). RESULTS: The current meta-analysis comprised 15 studies with a total of 11.365 participants. High circulating PTX3 concentrations were associated with a higher risk of composite poor outcomes as compared to low circulating PTX3 concentrations (OR: 1.36 [1.18, 1.54], p < 0.001; I2 = 86.69%, Pheterogeneity<0.001), mortality (OR: 1.43 [1.15, 1.71], p < 0.001; I2 = 87.58%, Pheterogeneity<0.001), and MACEs (OR: 1.28 [1.08, 1.48], p < 0.001; I2 = 35.86%, Pheterogeneity = 0.08) in patients with CAD. Consistent results were obtained during meta-regression analyses and in all examined subgroups. The adjusted odds ratios (aORs) for composite poor outcomes increased by 32% per 1 ng/mL increment (OR: 1.32 [1.21, 1.43]) in line with the dose-response meta-analysis. CONCLUSION: A significant positive dose-dependent association between circulating PTX3 concentration and the risk of poor outcomes in patients with CAD was found in this dose-response meta-analysis.

Increased Levels of serum Pentraxin 3 in Critical Coronavirus Disease-2019 Patients.

Pentraxin 3 (PTX3) and ficolin are the plasma phase of pattern recognition receptors (PRRs) and can activate complement through classical and lectin pathways, respectively, which may contribute to disease severity. This study aimed to investigate the association between PTX3 and ficolin with disease severity in patients with coronavirus disease-2019 (COVID-19). Seventy-three COVID-19 patients and 25 healthy controls were enrolled in this study. The participants were divided into three groups as follows: 14 patients as the intensive care unit (ICU) group, 59 patients as the non-ICU group, and 25 subjects as the healthy control group. The serum levels of PTX3 and ficolin were measured by enzyme-linked immunosorbent assay (ELISA) kits. Patients in ICU and non-ICU groups had significantly higher levels of PTX3 compared to the healthy control group (p = 0.0002 and p = 0.0072, respectively). Patients in the ICU group also had an increased amount of PTX3 (1957 ± 1769 pg/ml) compared to non-ICU patients (1220 ± 1784 pg/ml). However, this difference was not significant. On the other hand, serum levels of ficolin were not different among the three groups. PTX3, as an acute phase protein, may contribute to disease severity. Its probable inflammatory role could result from the high activation of the complement system. On the other hand, it could be suggested that ficolin has no crucial role in the disease severity of COVID-19 patients.