Pentraxin 3 in Cardiovascular Disease Ristagno, Giuseppe; Fumagalli, Francesca; Bottazzi, Barbara ...
Frontiers in immunology,
04/2019, Volume:
10
Journal Article
Peer reviewed
Open access
The long pentraxin PTX3 is a member of the pentraxin family produced locally by stromal and myeloid cells in response to proinflammatory signals and microbial moieties. The prototype of the pentraxin ...family is C reactive protein (CRP), a widely-used biomarker in human pathologies with an inflammatory or infectious origin. Data so far describe PTX3 as a multifunctional protein acting as a functional ancestor of antibodies and playing a regulatory role in inflammation. Cardiovascular disease (CVD) is a leading cause of mortality worldwide, and inflammation is crucial in promoting it. Data from animal models indicate that PTX3 can have cardioprotective and atheroprotective roles regulating inflammation. PTX3 has been investigated in several clinical settings as possible biomarker of CVD. Data collected so far indicate that PTX3 plasma levels rise rapidly in acute myocardial infarction, heart failure and cardiac arrest, reflecting the extent of tissue damage and predicting the risk of mortality.
Amongst psychiatric disorders, major depressive disorder (MDD) is the most prevalent, by affecting approximately 15-17% of the population and showing a high suicide risk rate equivalent to around ...15%. The present comprehensive overview aims at evaluating main research studies in the field of MDD at suicide risk, by proposing as well as a schematic suicide risk stratification and useful flow-chart for planning suicide preventive and therapeutic interventions for clinicians.
A broad and comprehensive overview has been here conducted by using PubMed/Medline, combining the search strategy of free text terms and exploded MESH headings for the topics of 'Major Depressive Disorder' and 'Suicide' as following: ((suicide Title/Abstract) AND (major depressive disorder Title/Abstract)). All articles published in English through May 31, 2019 were summarized in a comprehensive way.
Despite possible pathophysiological factors which may explain the complexity of suicide in MDD, scientific evidence supposed the synergic role of genetics, exogenous and endogenous stressors (i.e., interpersonal, professional, financial, as well as psychiatric disorders), epigenetic, the hypothalamic-pituitary-adrenal stress-response system, the involvement of the monoaminergic neurotransmitter systems, particularly the serotonergic ones, the lipid profile, neuro-immunological biomarkers, the Brain-derived neurotrophic factor and other neuromodulators.
The present overview reported that suicide is a highly complex and multifaceted phenomenon in which a large plethora of mechanisms could be variable implicated, particularly amongst MDD subjects. Beyond these consideration, modern psychiatry needs a better interpretation of suicide risk with a more careful assessment of suicide risk stratification and planning of clinical and treatment interventions.
Sepsis, a leading cause of death in critically ill patients, is the result of complex interactions between the infecting microorganisms and the host responses that influence clinical outcomes. We ...evaluated the prognostic value of presepsin (sCD14-ST), a novel biomarker of bacterial infection, and compared it with procalcitonin (PCT).
This is a retrospective, case-control study of a multicenter, randomized clinical trial enrolling patients with severe sepsis or septic shock in ICUs in Italy. We selected 50 survivors and 50 non-survivors at ICU discharge, matched for age, sex and time from sepsis diagnosis to enrollment. Plasma samples were collected 1, 2 and 7 days after enrollment to assay presepsin and PCT. Outcome was assessed 28 and 90 days after enrollment.
Early presepsin (day 1) was higher in decedents (2,269 pg/ml, median (Q1 to Q3), 1,171 to 4,300 pg/ml) than in survivors (1,184 pg/ml (median, 875 to 2,113); P = 0.002), whereas PCT was not different (18.5 μg/L (median 3.4 to 45.2) and 10.8 μg/L (2.7 to 41.9); P = 0.31). The evolution of presepsin levels over time was significantly different in survivors compared to decedents (P for time-survival interaction = 0.03), whereas PCT decreased similarly in the two groups (P = 0.13). Presepsin was the only variable independently associated with ICU and 28-day mortality in Cox models adjusted for clinical characteristics. It showed better prognostic accuracy than PCT in the range of Sequential Organ Failure Assessment score (area under the curve (AUC) from 0.64 to 0.75 vs. AUC 0.53 to 0.65).
In this multicenter clinical trial, we provide the first evidence that presepsin measurements may have useful prognostic information for patients with severe sepsis or septic shock. These preliminary findings suggest that presepsin may be of clinical importance for early risk stratification.
Prognostic Value of Changes in N-Terminal Pro-Brain Natriuretic Peptide in Val-HeFT (Valsartan Heart Failure Trial) Serge Masson, Roberto Latini, Inder S. Anand, Simona Barlera, Laura Angelici, ...Tarcisio Vago, Gianni Tognoni, Jay N. Cohn, for the Val-HeFT Investigators We assessed the prognostic value of repeated determinations of N-terminal pro-brain natriuretic peptide (NT-proBNP) in a large population of patients with stable and chronic heart failure (HF). A single determination of NT-proBNP showed a higher prognostic discrimination during the course of a strict clinical monitoring period than continuous changes of concentrations. Categorical changes across a threshold value predicted outcome independently of a single determination. Serial determinations of NT-proBNP and classification into few categories of changes may be a superior strategy for risk stratification of patients with chronic and stable HF, and may offer an aid in monitoring these patients.
The renin-angiotensin system plays a role in the etiology of hypertension and the pathophysiology of cardiac and renal diseases in humans. Ang II is the central product of this system and is involved ...in regulating immune responses, inflammation, cell growth, and proliferation by acting through Ang II type 1 receptors (AT1 and AT2). Here, we show that targeted disruption of the Agtr1a gene that encodes AT1A results in marked prolongation of life span in mice. Agtr1a-/- mice developed less cardiac and vascular injury, and multiple organs from these mice displayed less oxidative damage than wild-type mice. The longevity phenotype was associated with an increased number of mitochondria and upregulation of the prosurvival genes nicotinamide phosphoribosyltransferase (Nampt) and sirtuin 3 (Sirt3) in the kidney. In cultured tubular epithelial cells, Ang II downregulated Sirt3 mRNA, and this effect was inhibited by an AT1 antagonist. These results demonstrate that disruption of AT1 promotes longevity in mice, possibly through the attenuation of oxidative stress and overexpression of prosurvival genes, and suggests that the Ang II/AT1 pathway may be targeted to influence life span in mammals.
Post-traumatic stress disorder (PTSD) is a common psychiatric disorder resulting from a traumatic event, is manifested through hyperarousal, anxiety, depressive symptoms, and sleep disturbances. ...Despite several therapeutic approaches being available, both pharmacological and psychological, recently a growing interest has developed in using cannabis and synthetic cannabinoids stems from their consideration as more efficient and better tolerated alternatives for the treatment of this condition. The present paper aims to evaluate the clinical and therapeutic potentials of medical cannabis and synthetic cannabinoids in treating PTSD patients.
A systematic electronic search was performed, including all papers published up to May 2019, using the following keywords (((cannabisTitle/Abstract) OR (synthetic cannabinoids Title/Abstract)) AND ((PTSDTitle/Abstract) OR (Posttraumatic stress disorderTitle/Abstract))) for the topics 'Cannabis', 'Synthetic Cannabinoids', 'PTSD', and MESH terms, on the PubMed, Cochrane Library, and Web of Science online databases. For data gathering purposes, PRISMA guidelines were followed. Results were organized into two groups, considering cannabis and synthetic cannabinoids as different therapeutic approaches for PTSD.
Present data show that cannabis and synthetic cannabinoids, both acting on the endocannabinoids system, may have a potential therapeutic use for improving PTSD symptoms, e.g., reducing anxiety, modulating memory-related processes, and improving sleep.
Even though the current literature suggests that cannabis and synthetic cannabinoids may have a role in the treatment of PTSD, there is currently limited evidence regarding their safety and efficacy. Therefore, additional research is needed in order to better understand the effectiveness and therapeutic usage of these drug classes and monitor their safety.
Coronary artery disease (CAD) is a major challenge in patients with type 2 diabetes (T2D). Coronary computed tomography angiography (CCTA) provides a detailed anatomic map of the coronary ...circulation. Proteomics are increasingly used to improve diagnostic and therapeutic algorithms. We hypothesized that the protein panel is differentially associated with T2D and CAD.
In CAPIRE (Coronary Atherosclerosis in Outlier Subjects: Protective and Novel Individual Risk Factors Evaluation-a cohort of 528 individuals with no previous cardiovascular event undergoing CCTA), participants were grouped into CAD
(clean coronaries) and CAD
(diffuse lumen narrowing or plaques). Plasma proteins were screened by aptamer analysis. Two-way partial least squares was used to simultaneously rank proteins by diabetes status and CAD.
Though CAD
was more prevalent among participants with T2D (HbA
6.7 ± 1.1%) than those without diabetes (56 vs. 30%,
< 0.0001), CCTA-based atherosclerosis burden did not differ. Of the 20 top-ranking proteins, 15 were associated with both T2D and CAD, and 3 (osteomodulin, cartilage intermediate-layer protein 15, and HTRA1) were selectively associated with T2D only and 2 (epidermal growth factor receptor and contactin-1) with CAD only. Elevated renin and GDF15, and lower adiponectin, were independently associated with both T2D and CAD. In multivariate analysis adjusting for the Framingham risk panel, patients with T2D were "protected" from CAD if female (
= 0.007), younger (
= 0.021), and with lower renin levels (
= 0.02).
We concluded that
) CAD severity and quality do not differ between participants with T2D and without diabetes;
) renin, GDF15, and adiponectin are shared markers by T2D and CAD;
) several proteins are specifically associated with T2D or CAD; and
) in T2D, lower renin levels may protect against CAD.
The biological role of adrenomedullin (ADM), a hormone involved in hemodynamic homeostasis, is controversial in sepsis because administration of either the peptide or an antibody against it may be ...beneficial.
Plasma biologically active ADM (bio-ADM) was assessed on days 1, 2, and 7 after randomization of 956 patients with sepsis or septic shock to albumin or crystalloids for fluid resuscitation in the multicenter Albumin Italian Outcome Sepsis trial. We tested the association of bio-ADM and its time-dependent variation with fluid therapy, vasopressor administration, organ failures, and mortality.
Plasma bio-ADM on day 1 (median Q1-Q3, 110 59-198 pg/mL) was higher in patients with septic shock, associated with 90-day mortality, multiple organ failures and the average extent of hemodynamic support therapy (fluids and vasopressors), and serum lactate time course over the first week. Moreover, it predicted incident cardiovascular dysfunction in patients without shock at enrollment (OR 95% CI, 1.9 1.4-2.5; P < .0001, for an increase of 1 interquartile range of bio-ADM concentration). bio-ADM trajectory during the first week of treatment clearly predicted 90-day mortality after adjustment for clinically relevant covariates (hazard ratio 95% CI, 1.3 1.2-1.4; P < .0001), and its reduction below 110 pg/mL at day 7 was associated with a marked reduction in 90-day mortality. Changes over the first 7 days of bio-ADM concentrations were not dependent on albumin treatment.
In patients with sepsis, the circulating, biologically active form of ADM may help individualizing hemodynamic support therapy, while avoiding harmful effects. Its possible pathophysiologic role makes bio-ADM a potential candidate for future targeted therapies.
ClinicalTrials.gov; No.: NCT00707122.
Objectives
to test the safety and efficacy of intravascular imaging and specifically optical coherence tomography (OCT) as a diagnostic tool for left main angioplasty and analyze the mid‐term outcome ...accordingly.
Background
Clinical data and international guidelines recommend the use of intravascular imaging ultrasound (IVUS) to guide left main (LM) angioplasty. Despite early experience using OCT in this setting is encouraging, the evidence supporting its use is still limited.
Methods
ROCK II is a multicenter, investigator‐driven, retrospective European study to compare the performance of IVUS and OCT versus angiography in patients undergoing distal‐LM stenting. The primary study endpoint was target‐lesion failure (TLF) including cardiac death, target‐vessel myocardial infarction and target‐lesion revascularization. We designed this study hypothesizing the superiority of intravascular imaging over angiographic guidance alone, and the non‐inferiority of OCT versus IVUS.
Results
A total of 730 patients, 377 with intravascular‐imaging guidance (162 OCT, 215 IVUS) and 353 with angiographic guidance, were analyzed. The one‐year rate of TLF was 21.2% with angiography and 12.7% with intravascular‐imaging (p = 0.039), with no difference between OCT and IVUS (p = 0.26). Intravascular‐imaging was predictor of freedom from TLF (HR 0.46; 95% CI 0.23–0.93: p = 0.03). Propensity‐score matching identified three groups of 100 patients each with no significant differences in baseline characteristics. The one‐year rate of TLF was 16% in the angiographic, 7% in the OCT and 6% in the IVUS group, respectively (p = 0.03 for IVUS or OCT vs. angiography). No between‐group significant differences in the rate of individual components of TLF were found.
Conclusions
Intravascular imaging was superior to angiography for distal LM stenting, with no difference between OCT and IVUS.
Little is known of the prognostic significance of mitral regurgitation (MR) on transcatheter aortic valve replacement (TAVR), the impact of TAVR on MR severity, and the variables associated with ...possible post-TAVR improvement in MR. We evaluated these issues in a multicenter registry of patients undergoing CoreValve Revalving System-TAVR.
Among 1007 consecutive patients, 670 (66.5%), 243 (24.1%), and 94 (9.3%) presented with no/mild, moderate, and severe MR, respectively. At 1 month after TAVR, patients with severe or moderate MR showed comparable mortality rates (odds ratio, 1.1; 95% confidence interval 95% CI, 0.7-1.55; P=0.2), but both were significantly higher compared with patients with mild/no MR (odds ratio, 2.2; 95% CI, 1.78-3.28; P<0.001; and odds ratio, 1.9; 95% CI, 1.1-3.3; P=0.02, respectively). One-year mortality was also similar between patients with severe and those with moderate MR (hazard ratio, 1.4; 95% CI, 0.94-2.4; P=0.06) and still significantly higher compared with patients with mild/no MR (hazard ratio, 1.7; 95% CI, 1.2-3.41; P<0.001; and hazard ratio, 1.4; 95% CI, 1.2-2.2; P=0.03, respectively). Severe pulmonary hypertension, atrial fibrillation, and MR more than mild, but not an improvement of ≥1 grade in MR severity, were independent predictors of mortality at 1 year. At 1 year, an improved MR was observed in 47% and 35% of patients with severe and moderate MR, respectively. The rate of low implantation was consistent across groups with improved, unchanged, or worsened MR. A functional type of MR and the absence of severe pulmonary hypertension and atrial fibrillation independently predicted the improvement in MR severity.
Baseline MR greater than mild is associated with higher mortality after CoreValve Revalving System-TAVR. A significant improvement in MR was more likely in patients with functional MR and without severe pulmonary hypertension or atrial fibrillation. The improvement in MR did not independently predict mortality.
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