Plasma C-reactive Protein Levels Research Articles

Endothelial function and concentrations of high-sensitivity C-reactive protein, interleukin-6, and tumor necrosis factor-alpha during a long agonist IVF protocol

We examined possible changes in endothelial function during a long agonist in vitro fertilization (IVF) protocol. We measured flow-mediated dilatation (FMD) and FMD percent (FMD%) from the brachial artery and plasma levels of high-sensitivity C-reactive protein (hsCRP), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-〈). We studied longitudinally three time points in 27 women undergoing a long agonist IVF treatment at Kuopio University Hospital. The first visit was at the beginning of their period (low estradiol). The other two visits were during gonadotrophin-releasing hormone (GnRH) analog downregulation (low estradiol) and at the end of follicle-stimulating hormone (FSH) stimulation (high estradiol). The first visit was used as the reference, and the women served as their own controls. During the stimulation protocol, FMD and FMD% remained. Toward the end of stimulation, hsCRP (P = 0.003), IL-6 (P = 0.04), and TNF-〈 (P = 0.008) concentrations all decreased, while estradiol levels increased (P < 0.001). Correlations between estradiol and proinflammatory factors or FMD were, however, non-significant. The only significant correlation appeared between FMD% and hsCRP at Visit 2 (r = 0.485, P = 0.01). In conclusion, IVF stimulation promoted no change in endothelial function, whereas hsCRP, IL-6, and TNF-〈 decreased. These findings indicate that estrogen may improve the cytokine profile among healthy women undergoing IVF, but this is not reflected in endothelial function.

Reappraising the role of baseline plasma C-reactive protein levels on recurrence after catheter ablation of persistent atrial fibrillation: insight from EARNEST-PVI trial

Abstract Background Subclinical inflammation is an important pathogenesis of developing and sustaining atrial fibrillation (AF). Because AF itself contribute to the inflammatory response, the role of baseline subclinical inflammation on AF recurrence after catheter ablation (CA) remains controversial in patients with persistent AF. Purpose To evaluate whether baseline plasma C-reactive protein (CRP) levels, a sensitive marker of inflammation, are associated with AF recurrence following CA. Methods The analysis was performed from the EARNEST-PVI trial, a randomized controlled trial designed to assess a CA strategy for persistent AF, which was conducted in the Osaka region of Japan. A total of 441 patients (median age, 67 years; 26% female; 25% long-standing persistent AF) whose plasma CRP levels were measured at baseline were included in this study. Results At baseline, a median (interquartile range) of plasma CRP level was 0.10 [0.06–0.19] mg/dl. Plasma CRP levels significantly increased at discharge (0.83 [0.21–1.84] mg/dl, p&amp;lt;0.001) and decreased 1 year after CA (0.10 [0.05–0.20] mg/dl, p=0.040) compared to the baseline value. During the follow-up of 1 year, 115 patients (26%) experienced AF recurrence, and the incidence was significantly higher in 124 patients with low CRP levels at baseline (cut-off ≤0.06 mg/dl) than the other 317 patients (33.9% vs. 23.0%, p=0.017). After adjustment of age, gender, body mass index, long-standing persistent AF, CA strategy, and plasma brain natriuretic peptide levels, low plasma CRP levels was a significant predictor of AF recurrence (hazard ratio, 1.51; 95% confidence interval, 1.02–2.24; p=0.042). Conclusions Low plasma CRP levels at baseline predicted AF recurrence in the EARNEST-PVI trial. Reappraising the role of CRP on AF recurrence may be needed in patients with persistent AF. Funding Acknowledgement Type of funding sources: Private company. Main funding source(s): Johnson &amp; Johnson KK

Telmisartan for treatment of Covid-19 patients: an open randomized clinical trial

Abstract Background The imbalance of the Renin Angiotensin System in favor of the angiotensin II has been described in Covid-19-patients. Angiotensin II regulates life processes, such as cell growth and division and can promote apoptosis initiating an inflammatory process with release of proinflammatory cytokines. Angiotensin receptor blockers (ARBs) block the AT1 receptor and could have a beneficial effect reducing Covid-19 inflammation. Purpose To assess whether Telmisartan is effective in reducing C-reactive protein (CRP) plasma levels in hospitalized patients with Covid-19, and improves clinical outcomes and length of stay and morbimortality. Trial design This is a parallel-group, randomized, two-arm, open-label, multicenter superiority trial with 1:1 allocation ratio. Methods Inclusion criteria: patients aged more than 18 years with less than 5 days of symptoms onset and after informed consent was obtained. Exclusion criteria: Patients admitted to intensive care unit (ICU) or using mechanical ventilatory support or ongoing ARBs / angiotensin-converting enzyme inhibitors treatment at the time of randomization. Control arm received standard care alone and treatment arm Telmisartan 80 mg bid 14 days added to standard care. Primary outcome were CRP plasma levels at day 5 and 8 after randomization. Secondary outcomes included time to discharge at 15 days, admission to ICU and death at 15 and 30 days. Results 158 patients were included in the analysis, 80 in the control and 78 in the telmisartan group. Day 5 control-group CRP levels were 6.06±6.95 mg/dL (n=66) while telmisartan group were 3.83±5.08 mg/dL (mean±SD; n=66, p&amp;lt;0.05). Day 8 CRP levels were 6.30±8.19 mg/dL (n=44) and 2.37±3.47 mg/dl (mean±SD; n=43, p&amp;lt;0.05) in the control and telmisartan groups, respectively. Kaplan-Meier analysis showed that Telmisartan-treated patients had lower median time to discharge (control=15 days; telmisartan=9 days). Death by day 30 was reduced by 81% in the telmisartan-treated group (control 22.54%, 16/71; telmisartan 4.29%, 3/70 participants; p=0.0023). Composite ICU, mechanical ventilation or death was reduced by telmisartan treatment at days 15 and 30. No telmisartan-related adverse events were reported. Conclusions Telmisartan, an inexpensive safe drug, in high doses, demonstrated anti-inflammatory effects and reduced morbimortality in Covid-19-hospitalized patients. Funding Acknowledgement Type of funding sources: Public hospital(s). Main funding source(s):Hospital Escuela José de San Martín, ArgentinaHospital Español de Buenos Aires, Argentina Probability of discharge up to

Dyslipidemia’s influence on the secretion ovarian’s steroids in female mice

Introduction: The synthesis ovarian’s steroids is a process thats depends on the supply of cholesterol. Objective: to evaluate the influence of dyslipidemia on the secretion ovarian’s steroids. Methodology: wild female mice were used (C57BL6) and LDL (LDLR-/-), which they were separated into 4 groups (n = 10): WTS: fed a standard diet; WTHL: fed a high-fat diet; KOS: fed a standard diet; KOHL: fed a high-fat diet. After 60 days, the estrous cycle was analyzed and after anesthetized, blood was collected for the to assess the lipid profile, glucose, plasma insulin level and HOMA index was calculated. In addition, plasma levels of C-reactive protein, estrogen and progesterone were determined. Results: The hyperlipidic diet in both the WTHL and the KOHL group generated hypercholesterolemia when compared to the WTS and KOS, respectively, with a decrease in HDLc, associated with an increase in CRP levels. Severe hypercholesterolemia in the KOHL group generated insulin resistance, marked by an increase in HOMAir. Food hypercholesterolemia in the WTHL group, food and genetics in the KOHL group, compared to their WTS and KOS controls, was definitive in reducing plasma levels of estrogen and progesterone. The genetic hypercholesterolemia associated with insulin resistance observed in the KOS and KOHL groups reduced the levels of progesterone, this reduction being more severe in the KOHL group, which had the highest HOMAir. Conclusion: dyslipidemia affected ovarian steroidogenesis in mice by means of oxidative stress, inflammation and insulin resistance and / or by decreasing HDL cholesterol levels.

Plasma PCSK9 levels increase following percutaneous coronary interventions

Abstract Background Beside its role in cholesterol homeostasis, Proprotein Convertase Subtilisin/Kexin type 9 (PCSK9) has been associated with the processes of vascular inflammation and atherosclerosis. The protein is expressed in endothelial cells, smooth muscle cells and macrophages and it is detected inside the human atherosclerotic plaque. Purpose We aimed to investigate the effect of acute inflammation associated with plaque rupture and vascular injury during elective percutaneous coronary intervention (PCI) on plasma levels of PCSK9 in patients with coronary artery disease (CAD). Methods We measured PCSK9, C-reactive protein (CRP), Interleukin-6 (IL-6) and high-sensitivity cardiac Troponin T (hs-cTnT) plasma levels immediately before and 18–24 hours after PCI via the radial approach, in 68 consecutive patients with stable CAD referred for elective PCI of a de novo lesion in a native coronary artery. Patients with unstable coronary syndrome &amp;lt;3 months old, baseline inflammatory condition, malignancy, auto-immune disease or intervention via the femoral access, were excluded. Results All patients were treated with balloon angioplasty and implantation of a second-generation drug eluting stent (DES). Baseline plasma levels of PCSK9 were higher in women and in patients treated with statins. At 18–24 hours after the procedure, plasma levels of PCSK9, CRP, IL-6 and hs-cTnT increased significantly compared to baseline (table). The change (elevation) in CRP plasma levels was statistically correlated with that of IL-6 (r=0.33; p=0.006) and with that of hs-cTnT (r=0.28; p=0.023). However, there was no correlation between the change (elevation) in plasma PCSK9 levels and those of IL-6 (r=−0.09; p=0.47), CRP (r=0.01; p=0.9), and hs-cTnT (r=0.1; p=0.41). Conclusions Plasma levels of PCSK9 increased by 26% following PCI with DES. That elevation was however, not correlated with the degree of myocardial injury (hs-cTnT) or of inflammation (IL-6 and CRP). The mechanism underlying PCK9 elevation post PCI requires further investigation. Funding Acknowledgement Type of funding sources: None.

Effect of the renin angiotensin system inhibitors on inflammatory markers: a systematic review and meta-analysis of 32 randomized controlled trials

Abstract Background Inflammation plays a critical role in the etiology of cardiovascular disease (CVD). The renin-angiotensin system inhibitors including angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) have been shown to be effective in reducing elevated blood pressure. However, the information on their potential effect on inflammatory markers including C-reactive protein (CRP), tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6) is still lacking. Purpose We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) to synthesize evidence about effect of ACEIs and ARBs on selected inflammatory markers. Methods PubMed, Scopus, and Embase were searched from inception until February 15, 2021. We included RCTs that assessed the effect of ACEIs or ARBs, compared with placebo, on any of the following markers: CRP, IL-6, or TNF-α. Mean changes in the relevant markers levels were pooled as a standardized mean difference (SMD) with a 95% confidence interval (CI) under the random-effects model. Heterogeneity was assessed using I2 and χ2 tests. Results Thirty-two RCTs (n=3,403 patients) were included in the analysis. Overall pooled analysis suggested that ACEIs significantly reduced plasma levels of CRP (SMD: −1.08 [95% CI: −1.57 to −0.59]; I2: 95%), IL-6 (SMD: −0.75 [95% CI: −1.41 to −0.09]; I2: 81%), and TNF-α (SMD: −1.77 [95% CI: −2.82 to −0.73]; I2: 95%). This lowering effect remained statistically significant by perindopril in terms of all relevant markers, by quinapril and ramipril in terms of IL-6 and by enalapril in terms of TNF-α. As for the ARBs as a class, they showed a statistically significant reduction only in terms of CRP (SMD: −0.14 [95% CI: −0.28 to −0.01]; I2: 0%) and did not significantly affect any of the other markers. Moreover, the ARBs individual drugs did not show any significant effect on any of the relevant markers except for valsartan that significantly reduced plasma levels of IL-6 (SMD: −0.42 [95% CI: −0.80 to −0.04]; I2: 0%). Conclusions Based on the results of this meta-analysis, ACEIs showed a beneficial lowering effect on CRP, IL-6, and TNF-α, while ARBs were effective as a class only in terms of CRP reduction. Further larger RCTs are warranted to confirm these results particularly in case of individual drugs and to assess the significance of these reductions in terms of CVD prevention. Funding Acknowledgement Type of funding sources: None.

Preclinical Markers in Inflammatory Bowel Disease. A Nested Case-Control Study.

Our objective was to determine if patients who later develop inflammatory bowel disease (IBD) show signs of increased inflammatory activity in plasma measured with high sensitivity C-reactive protein (CRP), calprotectin, and albumin before the clinical onset of IBD. We identified 96 subjects who later developed IBD (70 ulcerative colitis [UC] and 26 Crohn's disease [CD]). High sensitivity CRP, calprotectin, and albumin were analyzed in frozen plasma, donated from cases and sex-age matched controls 1-15 years before diagnosis. We found that subjects who later developed UC had lower albumin levels, and subjects who later developed CD had higher CRP levels than controls. Multivariable conditional logistic regression with albumin, calprotectin, and CRP showed a lower risk for developing IBD and UC with higher albumin levels (odds ratio [OR] 0.79, confidence interval [CI] 0.69-0.90; respective OR 0.77, CI 0.66-0.91). Higher CRP levels were associated with an increased risk of developing CD (OR 1.314, CI 1.060-1.630). When adjusting for body mass index or smoking in the logistic regression model, similar results were found. Plasma calprotectin levels in the preclinical period among patients with IBD did not differ from controls. In this nested case-control study, subjects who later developed IBD had signs of low-grade systemic inflammation, indicated by significantly higher CRP plasma levels in CD and lower albumin plasma levels in UC, before the onset of clinical disease.

Biochemical predictors for Sars-Cov-2 severity.

It is of interest to assess the inflammatory marker profile in SARS-CoV-2 patients and to correlate the levels of systemic inflammatory biomarkers such as neutrophil-to-lymphocyte ratio (NLR), C-Reactive Protein CRP, Ferritin, Creatine kinase (CK), Lactate dehydrogenase (LDH) and liver function analytes total serum proteins, albumin, total bilirubin, direct bilirubin, alkaline phosphatase, aspartate aminotransferase (AST) and alanine aminotransferase (ALT) with the severity of SARS-CoV-2 infections. A total of 1000 COVID-19 positive patient's data were collected. Laboratory assessments consisted of NLR (neutrophil-lymphocyte ratio) by cell counter, C Reactive Protein (CRP) by immunoturbidimetry, Ferritin by electrochemiluminescence (ECLIA) and Creatine Kinase (CK), Lactate Dehydrogenase (LDH), Alkaline phosphatase (ALP), Aspartate aminotransferase (AST), Alanine aminotransferase (ALT), Total Bilirubin, Direct Bilirubin, Total Protein and Albumin by spectrophotometry. The mean plasma CRP levels, NLR, ferritin, CK and LDH levels were higher in severe cases than in non-severe cases, and the difference was statistically significant (p<0.05). All liver function tests such as the total and direct bilirubin, AST, ALT, ALP, total protein and albumin were higher in severe patients than non-severe patients and the difference was statistically significant (p<0.05). Data indicate that NLR, CRP, Ferritin, CK, LDH and liver function analytes have a crucial role as prognostic markers for SARS-CoV-2 infections and hence should be routinely recommended for risk assessment and stratification of the patients to reduce the associated morbidity and mortality.

Mendelian randomisation and experimental medicine approaches to interleukin-6 as a drug target in pulmonary arterial hypertension.

BackgroundInflammation and dysregulated immunity are important in the development of pulmonary arterial hypertension (PAH). Compelling preclinical data supports the therapeutic blockade of interleukin-6 (IL-6) signalling.MethodsWe conducted a phase 2 open-label study of intravenous tocilizumab (8 mg·kg−1) over 6 months in patients with group 1 PAH. Co-primary end-points were safety, defined by incidence and severity of adverse events, and change in pulmonary vascular resistance. Separately, a mendelian randomisation study was undertaken on 11 744 individuals with European ancestry including 2085 patients with idiopathic/heritable disease for the IL-6 receptor (IL6R) variant (rs7529229), known to associate with circulating IL-6R levels.ResultsWe recruited 29 patients (male/female 10/19; mean±sd age 54.9±11.4 years). Of these, 19 had heritable/idiopathic PAH and 10 had connective tissue disease-associated PAH. Six were withdrawn prior to drug administration; 23 patients received at least one dose of tocilizumab. Tocilizumab was discontinued in four patients owing to serious adverse events. There were no deaths. Despite evidence of target engagement in plasma IL-6 and C-reactive protein levels, both intention-to-treat and modified intention-to-treat analyses demonstrated no change in pulmonary vascular resistance. Inflammatory markers did not predict treatment response. Mendelian randomisation did not support an effect of the lead IL6R variant on risk of PAH (OR 0.99, p=0.88).ConclusionAdverse events were consistent with the known safety profile of tocilizumab. Tocilizumab did not show any consistent treatment effect.

Circulating P2X7 Receptor Signaling Components as Diagnostic Biomarkers for Temporal Lobe Epilepsy.

Circulating molecules have potential as biomarkers to support the diagnosis of epilepsy and to assist with differential diagnosis, for example, in conditions resembling epilepsy, such as in psychogenic non-epileptic seizures (PNES). The P2X7 receptor (P2X7R) is an important regulator of inflammation and mounting evidence supports its activation in the brain during epilepsy. Whether the P2X7R or P2X7R-dependent signaling molecules can be used as biomarkers of epilepsy has not been reported. P2X7R levels were analyzed by quantitative ELISA using plasma samples from controls and patients with temporal lobe epilepsy (TLE) or PNES. Moreover, blood cell P2X7R expression and P2X7R-dependent cytokine signature was measured following status epilepticus in P2X7R-EGFP reporter, wildtype, and P2X7R-knockout mice. P2X7R plasma levels were higher in TLE patients when compared with controls and patients with PNES. Plasma levels of the broad inflammatory marker protein C-Reactive protein (CRP) were similar between the three groups. Using P2X7R-EGFP reporter mice, we identified monocytes as the main blood cell type expressing P2X7R after experimentally evoked seizures. Finally, cytokine array analysis in P2X7R-deficient mice identified KC/GRO as a potential P2X7R-dependent plasma biomarker following status epilepticus and during epilepsy. Our data suggest that P2X7R signaling components may be a promising subclass of circulating biomarkers to support the diagnosis of epilepsy.

The experience of an emergency intensive care unit during the COVID-19 pandemic: A retrospective cohort study

Aim: The availability of an intensive care unit in the emergency departments (EDICU) is one of the most important issues discussed recently in terms of increasing the quality of emergency patient care. In this study, we aimed to investigate the clinical characteristics and factors affecting the mortality in patients with COVID-19. Material and Methods: This is a retrospective study of patients with COVID-19 hospitalized in EDICU. Patients were divided into mortality and survival groups, and the clinical characteristics of these groups were compared. Results: A total of 38 patients were included;47.4% (n = 18) were in the survival group. Oxygen saturation level was significantly different between the mortality and survival groups [78.0% (63.7-83.0) vs 88.5% (81.5-93.2), p = 0.001]. Patients in the mortality group had higher plasma levels of lactate dehydrogenase (LDH), procalcitonin, C-reactive protein (CRP), lactate, ferritin and D-dimer. Univariate regression analysis showed that oxygen saturation, LDH, CRP and endotracheal intubation (ETI) were significant markers in predicting mortality (p = 0.011, p = 0.035, p <0.001, respectively). A CRP level ≥ 91.9 mg/L predicts mortality with a sensitivity of 66.6% and a specificity of 80.0% (AUC: 0.781, 95% CI: 0.617-0,898). Discussion: This study showed that oxygen saturation, ETI, LDH and CRP levels were significantly successful in predicting mortality. Therefore, early administration of antibiotherapy and timely use of ETI may increase the quality of patient care.

The Relationship between the Tissue Expression of TLR2, TLR4, TLR5, and TLR7 and Systemic Inflammatory Responses in Colorectal Cancer Patients

Background: Colorectal cancer (CRC) is the third most commonly diagnosed malignancy globally. CRC patients with elevated plasma C-reactive protein (CRP) levels exhibit compromised prognoses. Toll-like receptors (TLRs), activating the innate and adaptive immune systems, may contribute to pro- and antitumorigenic inflammatory responses. We aimed to identify a possible link between local and systemic inflammatory responses in CRC patients by investigating the association between tissue TLRs and plasma CRP. Methods: Tissue expressions of TLR2, TLR4, TLR5, and TLR7 were assessed using immunohistochemistry of tissue microarray slides from 549 CRC patients surgically treated between 1998 and 2005. Blood samples were drawn preoperatively, centrifuged, aliquoted, and stored at −80°C until analysis. Plasma CRP was determined through high-sensitivity time-resolved immunofluorometric assay. We investigated the association of TLRs to clinicopathologic variables, plasma CRP, and survival. Results: High TLR2 expression (hazard ratio [HR] 0.59; 95% confidence interval [CI] 0.41–0.85; p = 0.005), high TLR5 expression (HR 0.60; 95% CI 0.45–0.83; p = 0.002), positive TLR7 expression (HR 0.49; 95% CI 0.33–0.72; p < 0.001), and low CRP (HR 1.48; 95% CI 1.08–2.11; p = 0.017) were associated with a better prognosis. A high TLR2 immunoexpression was associated with a better prognosis among low-CRP patients (HR 0.53; 95% CI 0.35–0.80; p = 0.002), high TLR4 expression among high-CRP patients (HR 2.04; 95% CI 1.04–4.00; p = 0.038), high TLR5 expression among low-CRP patients (HR 0.059; 95% CI 0.37–0.92; p = 0.021), and positive TLR7 expression among low-CRP patients (HR 0.53; 95% CI 0.28–1.00; p = 0.049). In multivariate analyses, no biomarkers emerged as significant independent variables. Conclusions: High tissue TLR2, TLR5, and TLR7 levels were associated with a better prognosis. Among low-CRP patients, those with high TLR2, TLR5, and TLR7 immunoexpressions exhibited a better prognosis. Among high CRP patients, a high TLR4 immunoexpression was associated with a better prognosis.

Hyperbilirubinemia Maintained by Chronic Supplementation of Unconjugated Bilirubin Improves the Clinical Course of Experimental Autoimmune Arthritis

Rheumatoid arthritis (RA) is a chronic multisystem disease, therapy of which remains a challenge for basic research. The present work examined the effect of unconjugated bilirubin (UCB) administration in adjuvant-induced arthritis (AIA)—an experimental model, in which oxidative stress (OS), inflammation and inadequate immune response are often similar to RA. Male Lewis rats were randomized into groups: CO—control, AIA—untreated adjuvant-induced arthritis, AIA-BIL—adjuvant-induced arthritis administrated UCB, CO-BIL—control with administrated UCB. UCB was administered intraperitoneally 200 mg/kg of body weight daily from 14th day of the experiment, when clinical signs of the disease are fully manifested, to 28th day, the end of the experiment. AIA was induced by a single intradermal immunization at the base of the tail with suspension of Mycobacterium butyricum in incomplete Freund’s adjuvant. Clinical, hematologic, biochemical and histologic examinations were performed. UCB administration to animals with AIA lead to a significant decrease in hind paws volume, plasma levels of C-reactive protein (CRP) and ceruloplasmin, drop of leukocytes, lymphocytes, erythrocytes, hemoglobin and an increase in platelet count. UCB administration caused significantly lowered oxidative damage to DNA in arthritic animals, whereas in healthy controls it induced considerable oxidative damage to DNA. UCB administration also induced atrophy of the spleen and thymus in AIA and CO animals comparing to untreated animals. Histological signs of joint damage assessed by neutrophils infiltration and deposition of fibrin were significantly reduced by UCB administration. The effects of exogenously administered UCB to the animals with adjuvant-induced arthritis might be identified as therapeutic, in contrast to the effects of UCB administration in healthy animals rather classified as toxic.

Associations between childhood victimization, inflammatory biomarkers and psychotic phenomena in adolescence: A longitudinal cohort study

Exposure to victimization in childhood has been linked to the development of psychosis. However, little is known about how childhood victimization is translated into biological risk for psychosis. One possibility is via increased inflammation. This study aimed to investigate the association between childhood victimization, psychotic experiences (PEs) in adolescence and inflammatory markers using data from a general population cohort. Participants were 1,419 British-born children followed from birth to age 18 years as part of the Environmental Risk Longitudinal Twin Study. Childhood victimization was measured prospectively using multiple sources from birth to age 12 years. PEs were assessed during private interviews with participants at age 18 years for the period since age 12. Plasma C-reactive protein (CRP), interleukin-6 (IL-6), and soluble urokinase plasminogen activator receptor (suPAR) levels were measured from plasma samples collected from participants at 18 years. Young people with both PEs and childhood victimization were more likely to belong to a group with elevated suPAR, CRP and IL-6 levels at 18 years of age (OR = 3.34, 95% CI 1.69–6.59, p = 0.001) than those with no childhood victimization and without PEs. However, this association was attenuated when adjusted for other risk factors for elevated inflammation at age 18 (OR = 1.94, 95% CI 0.94–4.04, p = 0.075). In contrast, presence of PEs without childhood victimization was not significantly associated with age-18 inflammatory markers and neither was childhood victimization without PEs (all p’s greater than 0.05). The current study highlights that inflammatory dysregulation is mostly present in adolescents reporting PEs who also experienced childhood victimization, though this seemed to be largely due to concurrent inflammation-related risk factors.

Pathophysiology of Major Depression by Clinical Stages.

The comprehension of the pathophysiology of the major depressive disorder (MDD) is essential to the strengthening of precision psychiatry. In order to determine the relationship between the pathophysiology of the MDD and its clinical progression, analyzed by severity of the depressive symptoms and sleep quality, we conducted a study assessing different peripheral molecular biomarkers, including the levels of plasma C-reactive protein (CRP), serum mature brain-derived neurotrophic factor (mBDNF), serum cortisol (SC), and salivary cortisol awakening response (CAR), of patients with MDD (n = 58) and a control group of healthy volunteers (n = 62). Patients with the first episode of MDD (n = 30) had significantly higher levels of CAR and SC than controls (n = 32) and similar levels of mBDNF of controls. Patients with treatment-resistant depression (TRD, n = 28) presented significantly lower levels of SC and CAR, and higher levels of mBDNF and CRP than controls (n = 30). An increased severity of depressive symptoms and worse sleep quality were correlated with levels low of SC and CAR, and with high levels of mBDNF. These results point out a strong relationship between the stages clinical of MDD and changes in a range of relevant biological markers. This can assist in the development of precision psychiatry and future research on the biological tests for depression.

Azithromycin Reduces Markers of Vascular Damage in Pediatric Patients With Sickle Cell Disease.

BackgroundImmunomodulatory effects of macrolides in chronic inflammation are well known. In this study, we tested our hypothesis that azithromycin (AZT) can decrease inflammation in pediatric patients with sickle cell disease (SCD).MethodsThe use of AZT as an anti-inflammatory agent was evaluated in double-blind, placebo-controlled, cross-over study for 8 weeks of treatment with 8 weeks of washout. Blood samples were collected before (PRE) and after (POST) each 8-week treatment period. Repeated measures analysis of variance (ANOVA) with post hoc multiple comparison procedures and Chi-square test were used for statistical analysis of the data. Complete blood count, distribution of the lymphocyte subsets, and plasma levels of markers of vascular damage were analyzed.ResultsA significant decrease in the number of leucocytes and granulocytes was observed in AZT group following treatment. An opposite dynamic was observed in placebo group; numbers of granulocytes significantly increased at POST interval. All markers of vascular damage were reduced in AZT group at POST interval with overall significance (P = 0.026). The most prominent significant changes were observed in levels of myeloid-related protein 8/14 (MRP8/14), lipocalin A (NGAL), matrix metalloproteinases (MMP) 9, and insulin-like growth factor-binding protein (IGFBP) 4. Plasma level of C-reactive protein (CRP) was significantly decreased in AZT group as well.ConclusionsData suggested that AZT may be beneficial in management of microvascular injury in SCD.

A predictive regression model of the obesity-related inflammatory status based on gut microbiota composition.

Fecal microbiome disturbances are linked to different human diseases. In the case of obesity, gut microbiota seems to play a role in the development of low-grade inflammation. The purpose of the present study was to identify specific bacterial families and genera associated with an increased obesity-related inflammatory status, which would allow to build a regression model for the prediction of the inflammatory status of obese and overweight subjects based on fecal microorganisms. A total of 361 volunteers from the Obekit trial (65 normal-weight, 110 overweight, and 186 obese) were classified according to four variables: waist/hip ratio (≥0.86 for women and ≥1.00 for men), leptin/adiponectin ratio (LAR, ≥3.0 for women and ≥1.4 for men), and plasma C-reactive protein (≥2 mg/L) and TNF levels (≥0.85 pg/mL). An inflammation score was designed to classify individuals in low (those subjects who did exceed the threshold value in 0 or 1 variable) or high inflammatory index (those subjects who did exceed the threshold value in 2 or more variables). Fecal 16 S rRNA sequencing was performed for all participants, and differential abundance analyses for family and genera were performed using the MicrobiomeAnalyst web-based platform. Methanobacteriaceae, Christensenellaceae, Coriobacteriaceae, Bifidobacteriaceae, Catabacteriaceae, and Dehalobacteriaceae families, and Methanobrevibacter, Eggerthella, Gemmiger, Anaerostipes, and Collinsella genera were significantly overrepresented in subjects with low inflammatory index. Conversely, Carnobacteriaceae, Veillonellaceae, Pasteurellaceae, Prevotellaceae and Enterobacteriaceae families, and Granulicatella, Veillonella, Haemophilus, Dialister Parabacteroides, Prevotella, Shigella, and Allisonella genera were more abundant in subjects with a high inflammatory index. A regression model adjusted by BMI, sex, and age and including the families Coriobacteriaceae and Prevotellaceae and the genus Veillonella was developed. A microbiota-based regression model was able to predict the obesity-related inflammatory status (area under the ROC curve = 0.8570 ± 0.0092 Harrell's optimism-correction) and could be useful in the precision management of inflammobesity.

Association of Bariatric Surgery With Vascular Outcomes

Bariatric surgical weight loss is associated with reduced cardiovascular mortality; however, the mechanisms underlying this association are incompletely understood. To identify variables associated with vascular remodeling after bariatric surgery and to examine how sex, race, and metabolic status are associated with microvascular and macrovascular outcomes. This population-based longitudinal cohort included 307 individuals who underwent bariatric surgery. Participants were enrolled in the bariatric weight loss program at Boston Medical Center, a large, multi-ethnic urban hospital, with presurgical and postsurgical assessments. Data were collected from December 11, 2001 to August 27, 2019. Data were analyzed in September 2019. Bariatric surgery. Flow-mediated dilation (FMD) and reactive hyperemia (RH) (as measures of macrovascular and microvascular function, respectively) and clinical variables were measured preoperatively at baseline and at least once postoperatively within 12 months of the bariatric intervention. A total of 307 participants with obesity (mean [SD] age, 42 [12] years; 246 [80%] women; 199 [65%] White; mean [SD] body mass index, 46 [8]) were enrolled in this study. Bariatric surgery was associated with significant weight loss and improved macrovascular and microvascular function across subgroups of sex, race, and traditional metabolic syndrome (mean [SD] pre- vs postsurgery weight: 126 [25] kg vs 104 [25] kg; P < .001; mean [SD] pre- vs postsurgery FMD: 9.1% [5.3] vs 10.2% [5.1]; P < .001; mean [SD] pre- vs postsurgery RH: 764% [400] vs 923% [412]; P < .001). Factors associated with change in vascular phenotype correlated most strongly with adiposity markers and several metabolic variables depending on vascular territory (eg, association of weight change with change in RH: estimate, -3.2; 95% CI, -4.7 to -1.8; association of hemoglobin A1c with change in FMD: estimate, -0.5; 95% CI, -0.95 to -0.05). While changes in macrovascular function among individuals with metabolically healthy obesity were not observed, the addition of biomarker assessment using high-sensitivity C-reactive protein plasma levels greater than 2 mg/dL identified participants with seemingly metabolically healthy obesity who had low-grade inflammation and achieved microvascular benefit from weight loss surgery. The findings of this study suggest that bariatric intervention is associated with weight loss and favorable remodeling of the vasculature among a wide range of individuals with cardiovascular risk. Moreover, differences in arterial responses to weight loss surgery by metabolic status were identified, underscoring heterogeneity in physiological responses to adiposity change and potential activation of distinct pathological pathways in clinical subgroups. As such, individuals with metabolically healthy obesity represent a mixed population that may benefit from more refined phenotypic classification.

The association between plasma tryptophan catabolites and depression: The role of symptom profiles and inflammation

BackgroundTryptophan catabolites (“TRYCATs”) produced by the kynurenine pathway (KP) may play a role in depression pathophysiology. Studies comparing TRYCATs levels in depressed subjects and controls provided mixed findings. We examined the association of TRYCATs levels with 1) the presence of Major Depressive Disorder (MDD), 2) depressive symptom profiles and 3) inflammatory markers. MethodsThe sample from the Netherlands Study of Depression and Anxiety included participants with current (n = 1100) or remitted (n = 753) MDD DSM-IV diagnosis and healthy controls (n = 642). Plasma levels of tryptophan (TRP), kynurenine (KYN), kynurenic acid (KynA), quinolinic acid (QA), C-reactive protein (CRP), interleukin-6 (IL-6) and tumor necrosis factor (TNF) were measured. Atypical/energy-related symptom (AES), melancholic symptom (MS) and anxious-distress symptom (ADS) profiles were derived from questionnaires. ResultsAfter adjustment for age, sex, education, smoking status, alcohol consumption and chronic diseases, no significant differences in TRYCATs were found comparing MDD cases versus controls. The MS profile was associated (q < 0.05) with lower KynA (β = -0.05), while AES was associated with higher KYN (β = 0.05), QA (β = 0.06) and TRP (β = 0.06). Inflammatory markers were associated with higher KYN (CRP β = 0.12, IL-6 β = 0.08, TNF β = 0.10) and QA (CRP β = 0.21, IL-6 β = 0.12, TNF β = 0.18). Significant differences against controls emerged after selecting MDD cases with high (top 30%) CRP (KYN d = 0.20, QA d = 0.33) and high TNF (KYN d = 0.24; QA d = 0.39). ConclusionsTRYCATs levels were related to specific clinical and biological features, such as atypical symptoms or a proinflammatory status. Modulation of KP may potentially benefit a specific subset of depressed patients. Clinical studies should focus on patients with clear evidence of KP dysregulations.

Endothelium Activation Markers in Severe Hospitalized COVID-19 Patients: Role in Mortality Risk Prediction.

Introduction Endothelial damage and hypercoagulability are major players behind the hemostatic derangement of SARS-CoV-2 infection. Aim In this prospective study we assessed endothelial and inflammatory biomarkers in a cohort of COVID-19 patients, aiming to identify predictive factors of in-hospital mortality. Methods COVID-19 patients hospitalized in intensive care (ICU) and non-ICU units at 2 Bergamo (Italy) hospitals from March 23 to May 30, 2020, were enrolled. Markers of endothelium activation including von-Willebrand factor (vWF), soluble thrombomodulin (sTM), and fibrinolytic proteins (t-PA and PAI-1) were measured. Additionally, D-dimer, Fibrinogen, FVIII, nucleosomes, C reactive protein (CRP) and procalcitonin were assessed. Results Sixty-three (45 ICU, and 18 non-ICU) patients, with a median age of 62 years were analyzed. Increased plasma levels of D-dimer, FVIII, fibrinogen, nucleosomes, CRP, and procalcitonin were observed in the whole cohort. Extremely elevated vWF levels characterized all patients (highest values in ICU-subjects). After a median time of 30 days, death occurred in 13 (21%) patients. By multivariable analysis, vWF-activity, neutrophil-count and PaO2/FiO2 were significantly associated with death. Using these variables, a linear score with 3-risk groups was generated that provided a cumulative incidence of death of 0% in the low-, 32% in the intermediate-, and 78% in the high-risk group. Conclusions COVID-19-induced hemostatic abnormalities are exacerbated by the severity of the disease and strongly correlate with the inflammatory status, underlying the link between coagulation, endothelial activation, and inflammation. Our study provides evidence for a role of vWF, together with neutrophils and PaO2/FiO2, as a significant predictor of in-hospital mortality by SARSCoV-2 infection.