Systemic inflammation in dogs with advanced-stage heart failure.
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ABSTRACT:
SUBMITTER: Domanjko Petric A
PROVIDER: S-EPMC5866510 | biostudies-literature | 2018 Mar
REPOSITORIES: biostudies-literature
Publications
Systemic inflammation in dogs with advanced-stage heart failure.
Domanjko Petrič Aleksandra A Lukman Tajda T Verk Barbara B Nemec Svete Alenka A
Acta veterinaria Scandinavica 20180324 1
<h4>Background</h4>Although human studies have shown that inflammation plays a role in the development of congestive heart failure, scarce information exists on white blood cell count (WBC) and differential cell counts in various stages of heart failure in man and dogs. A few studies demonstrated increased concentrations of C-reactive protein (CRP), a major acute-phase protein, in cardiac diseases in dogs. Our research aimed to investigate whether CRP concentration, WBC and neutrophil count (NEU ...[more]
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Project description:BackgroundInflammation and oxidative stress can contribute to the development and progression of heart failure. This study aimed to investigate the association between inflammatory and oxidative stress markers in dogs with congestive heart failure (CHF). Associations between the disease severity marker N-terminal pro-B-type natriuretic peptide (NT-proBNP) and markers of inflammation and oxidative stress were also determined.ResultsThirty-seven dogs with cardiovascular diseases (dilated cardiomyopathy, DCM (16 dogs), myxomatous mitral valve disease, MMVD (21 dogs)) and ten healthy dogs were included in this prospective study. The patients were further divided into groups with (26) and without CHF (11). We found a significantly higher serum concentration of C-reactive protein (P = 0.012), white blood cell (P = 0.001), neutrophil (P = 0.001) and monocyte counts (P = 0.001) in patients with CHF compared to control dogs. The concentration of tumor necrosis factor-alpha (TNF-α) was significantly higher in patients with CHF compared to patients without CHF (P = 0.030). No significant difference was found in most of the measured parameters between MMVD and DCM patients, except for glutathione peroxidase (GPX) and NT-proBNP. In patients with CHF, TNF-α correlated positively with malondialdehyde (P = 0.014, r = 0.474) and negatively with GPX (P = 0.026, r = - 0.453), and interleukin-6 correlated negatively with GPX (P = 0.046, r = - 0.412). NT-proBNP correlated positively with malondialdehyde (P = 0.011, r = 0.493). In patients without CHF none of the inflammatory and oxidative stress markers correlated significantly. Furthermore, in the group of all cardiac patients, GPX activity significantly negatively correlated with NT-proBNP (P = 0.050, r = - 0.339) and several markers of inflammation, including TNF-α (P = 0.010, r = - 0.436), interleukin-6 (P = 0.026, r = - 0.382), white blood cell (P = 0.032, r = - 0.369), neutrophil (P = 0.027, r = - 0.379) and monocyte counts (P = 0.024, r = - 0.386).ConclusionInflammatory and oxidative stress markers are linked in canine CHF patients, but not in patients without CHF. These results suggest complex cross communication between the two biological pathways in advanced stages of CHF.
| S-EPMC8077822 | biostudies-literature
Project description:The Pediatric Acute Liver Failure (PALF) study is a multicenter, observational cohort study of infants and children diagnosed with this complex clinical syndrome. Outcomes in PALF reflect interactions among the child's clinical condition, response to supportive care, disease severity, potential for recovery, and, if needed, availability of a suitable organ for liver transplantation (LTx). Previously, we used computational analyses of immune/inflammatory mediators that identified three distinct dynamic network patterns of systemic inflammation in PALF associated with spontaneous survivors, non-survivors (NS), and LTx recipients. To date, there are no data exploring age-specific immune/inflammatory responses in PALF. Accordingly, we measured a number of clinical characteristics and PALF-associated systemic inflammatory mediators in daily serum samples collected over the first 7 days following enrollment from five distinct PALF cohorts (all spontaneous survivors without LTx): infants (INF, <1 year), toddlers (TOD, 1-2 years.), young children (YCH, 2-4 years), older children (OCH, 4-13 years) and adolescents (ADO, 13-18 years). Among those groups, we observed significant (P<0.05) differences in ALT, creatinine, Eotaxin, IFN-γ, IL-1RA, IL-1β, IL-2, sIL-2Rα, IL-4, IL-6, IL-12p40, IL-12p70, IL-13, IL-15, MCP-1, MIP-1α, MIP-1β, TNF-α, and NO2-/NO3- . Dynamic Bayesian Network inference identified a common network motif with HMGB1 as a central node in all sub-groups, with MIG/CXCL9 being a central node in all groups except INF. Dynamic Network Analysis (DyNA) inferred different dynamic patterns and overall dynamic inflammatory network complexity as follows: OCH>INF>TOD>ADO>YCH. Hypothesizing that systemically elevated but sparsely connected inflammatory mediators represent pathological inflammation, we calculated the AuCon score (area under the curve derived from multiple measures over time divided by DyNA connectivity) for each mediator, and identified HMGB1, MIG, IP-10/CXCl10, sIL-2Rα, and MCP-1/CCL2 as potential correlates of PALF pathophysiology, largely in agreement with the results of Partial Least Squares Discriminant Analysis. Since NS were in the INF age group, we compared NS to INF and found greater inflammatory coordination and dynamic network connectivity in NS vs. INF. HMGB1 was the sole central node in both INF and NS, though NS had more downstream nodes. Thus, multiple machine learning approaches were used to gain both basic and potentially translational insights into a complex inflammatory disease.
| S-EPMC7844097 | biostudies-literature
Project description:BackgroundMalignant ascites is prevalent in advanced-stage ovarian cancer and may facilitate identification of the drivers of muscle loss. This study aimed to evaluate the association of ascites with changes in systemic inflammation and muscle after treatment of advanced-stage ovarian cancer.MethodsWe evaluated 307 patients with advanced-stage (III/IVA) ovarian cancer who underwent primary debulking surgery and adjuvant platinum-based chemotherapy between 2010 and 2019. The changes in skeletal muscle index (SMI) and radiodensity (SMD) were measured using pre-surgery and post-chemotherapy portal-venous phase contrast-enhanced computed tomography scans at L3. Systemic inflammation was measured using albumin levels, prognostic nutritional index (PNI), neutrophil-lymphocyte ratio (NLR), and platelet-lymphocyte ratio (PLR). Primary endpoint was the changes in SMI and SMD after treatment. Linear regression analysis was used to test associations between muscle change and other covariates. Mediation analysis was used to determine the mediator.ResultsThe median (range) age was 53 (23-83) years. The median duration (range) of follow-up was 5.2 (1.1-11.3) years. Overall, 187 (60.9%) patients had ascites. The changes in muscle and systemic inflammatory markers after treatment were significantly different between patients with and without ascites (SMI: -3.9% vs. 2.2%, P < 0.001; SMD: -4.0% vs. -0.4%, P < 0.001; albumin: -4.4% vs. 2.1%, P < 0.001; PNI: -8.4% vs. -0.1%, P < 0.001; NLR: 20.6% vs. -29.4%, P < 0.001; and PLR: 1.7% vs. -19.4%, P < 0.001). The changes in SMI and SMD were correlated with the changes in albumin, PNI, NLR, and PLR (all P < 0.001). In multiple linear regression, ascites and NLR changes were negatively while albumin change was positively correlated with SMI change (ascites: β = -3.19, P < 0.001; NLR change: β = -0.02, P = 0.003; albumin change: β = 0.37, P < 0.001). Ascites and NLR changes were negatively while PNI change was positively correlated with SMD change (ascites: β = -1.28, P = 0.02; NLR change: β = -0.02, P < 0.001; PNI change: β = 0.11, P = 0.04). In mediation analysis, ascites had a direct effect on SMI change (P < 0.001) and an indirect effect mediated by NLR change (indirect effects = -1.61, 95% confidence interval [CI]: -2.22 to -1.08) and albumin change (indirect effects = -2.92, 95% CI: -4.01 to -1.94). Ascites had a direct effect on SMD change (P < 0.001) and an indirect effect mediated by NLR change (indirect effects = -1.76, 95% CI: -2.34 to -1.22) and PNI change (indirect effects = -2.00, 95% CI: -2.79 to -1.36).ConclusionsMalignant ascites was associated with enhanced systemic inflammation and muscle loss after primary debulking surgery and adjuvant chemotherapy in advanced-stage ovarian cancer. The association between ascites and muscle loss may be mediated by systemic inflammation.
| S-EPMC10570096 | biostudies-literature
Project description:Background: Platelets play a central role in the development of cardiovascular diseases and changes in their proteins are involved in the pathophysiology of heart diseases in humans. There is lack of knowledge about the possible role of platelets in congestive heart failure (CHF) in dogs. Thus, this study aimed to investigate the changes in global platelet proteomes in dogs with CHF, to clarify the possible role of platelets in the physiopathology of this disease. Healthy-dogs (n =?10) and dogs with acute CHF due to myxomatous mitral valve disease (MMVD, n?=?10) were used. Acute CHF was defined based on the clinical (increased respiratory rate or difficulty breathing) and radiographic findings of pulmonary edema. Dogs Blood samples were collected into tubes with acid-citrate-dextrose, and platelet-pellets were obtained by centrifuge and washing steps. Platelet-proteomes were identified using LC-MS based label-free differential proteome expression analysis method and matched according to protein database for Canis lupus familiaris.Results: Totally 104 different proteins were identified in the platelets of the dogs being 4 out of them were significantly up-regulated and 6 down-regulated in acute CHF dogs. Guanine-nucleotide-binding protein, apolipoproteins (A-II and C-III) and clusterin levels increased, but CXC-motif-chemokine-10, cytochrome-C-oxidase-subunit-2, cathepsin-D, serine/threonine-protein-phosphatase-PP1-gamma-catalytic-subunit, creatine-kinase-B-type and myotrophin levels decreased in acute CHF dogs. These proteins are associated with several molecular functions, biological processes, signaling systems and immune-inflammatory responses.Conclusion: This study describes by first time the changes in the protein composition in platelets of dogs with acute CHF due to MMVD. Our findings provide a resource for increase the knowledge about the proteome of canine platelets and their roles in CHF caused by MMVD and could be a tool for further investigations about the prevention and treatment of this disease.
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Project description:This study was carried out to investigate the prognostic utility of biomarkers in advanced stage heart failure (HF) patients requiring ICU admission for pulmonary artery catheter (PAC) guided therapy.Thirty patients admitted to an ICU for PAC guided HF therapy were enrolled; concentrations of soluble ST2 (sST2), highly sensitive troponin I, an experimental ultrasensitive troponin I, amino-terminal pro-B type natriuretic peptide, cystatin C, and myeloperoxidase were measured over the first 48 hours. Outcomes included response of filling pressures and hemodynamics to tailored therapy and 90-day event-free survival (death, left ventricular assist device implantation, transplant).Of the biomarkers evaluated, only sST2 concentrations were higher in those who failed to achieve goals for central venous pressure ((CVP), 225.3 versus 104.6 ng/mL; P = 0.003) and pulmonary capillary wedge pressure ((PCWP), 181.7 versus 88.2 ng/mL; P = 0.05). Only sST2 concentrations were associated with adverse events (186.7 versus 92.2 ng/mL; P = 0.01). In age-adjusted Cox proportional hazards analysis, an elevated sST2 during the first 48 hours following ICU admission independently predicted 90-day outcomes (Hazard Ratio = 5.53; P = 0.03) superior to the Simplified Acute Physiology Score for this application; in Kaplan-Meier analysis the risk associated with elevated sST2 concentrations was present early and sustained through the duration of follow-up (log rank P = 0.01).In patients undergoing HF therapy guided by invasive monitoring, sST2 concentrations were associated with impending failure to reduce filling pressures and predicted impending events. Elevated sST2 values early in the ICU course theoretically could assist therapeutic decision-making in advanced stage HF patients.ClinicalTrials.gov Identifier: NCT00595738.
| S-EPMC3580720 | biostudies-literature
Project description:This in-depth review of sex differences in advanced heart failure therapy summarizes the existing literature on implantable cardioverter defibrillators, biventricular pacemakers, mechanical circulatory support, and transplantation with a focus on utilization, efficacy/clinical effectiveness, adverse events, and controversies. One will learn about the controversies regarding efficacy/clinical effectiveness of implantable cardioverter defibrillators and understand why these devices should be implanted in women even if there are sex differences in appropriate shocks. Individuals will learn about the sex differences with biventricular pacemakers with respect to ventricular remodeling and reduction in heart failure hospitalizations/mortality, as well as, possible mechanisms. We will demonstrate sex differences in heart transplantation and waitlist survival. Despite similar survival for women and men with left ventricular assist devices, there are sex differences in adverse events. These devices do successfully bridge women and men to transplant, yet women are less likely than men to have a left ventricular assist at time of listing and time of transplantation. Finally, one will learn about the concerns regarding poor outcome for men who receive female donor hearts and discover this may not be due to sex, but rather size. More research is needed to better understand sex differences and further improve advanced heart failure therapy for both women and men.
| S-EPMC6383806 | biostudies-literature
Project description:BackgroundSarcopenia and inflammation have been associated with poor survival in patients with cancer. We explored the combined effects of these variables on survival in patients with cancer treated with immunotherapy.MethodsWe performed a retrospective review of 90 patients enrolled on immunotherapy-based phase I clinical trials at Emory University from 2009 to 2017. Baseline neutrophil-to-lymphocyte ratio, monocyte-to-lymphocyte ratio, and platelet-to-lymphocyte ratio (PLR) were used as surrogates of inflammation. The skeletal muscle index (SMI) was derived from the skeletal muscle density calculated from baseline abdominal computed tomography images. Optimal cutoffs for continuous inflammation biomarkers and SMI were determined by bias-adjusted log-rank test. A four-level risk stratification was used to create low-risk (PLR <242 and nonsarcopenic), intermediate-risk (PLR <242 and sarcopenic), high-risk (PLR ≥242 and nonsarcopenic), and very-high-risk (PLR ≥242 and sarcopenic) groups with subsequent association with survival.ResultsMost patients (59%) were male, and the most common cancers were melanoma (33%) and gastrointestinal (22%). Very high-risk, high-risk, and intermediate-risk patients had significantly shorter overall survival (hazard ratio [HR], 8.46; 95% confidence interval [CI], 2.65-27.01; p < .001; HR, 5.32; CI, 1.96-14.43; p = .001; and HR, 4.01; CI, 1.66-9.68; p = .002, respectively) and progression-free survival (HR, 12.29; CI, 5.15-29.32; p < .001; HR, 3.51; CI, 1.37-9.02; p = .009; and HR, 2.14; CI, 1.12-4.10; p = .022, respectively) compared with low-risk patients.ConclusionBaseline sarcopenia and elevated inflammatory biomarkers may have a combined effect on decreasing survival in immunotherapy-treated patients in phase I trials. These data may be immediately applicable for medical oncologists for the risk stratification of patients beginning immunotherapeutic agents.Implications for practiceSarcopenia and inflammation have been associated with poor survival in patients with cancer, but it is unclear how to apply this information to patient care. The authors created a risk-stratification system that combined sarcopenia and platelet-to-lymphocyte ratio as a marker of systemic inflammation. The presence of sarcopenia and systemic inflammation decreased progression-free survival and overall survival in our cohort of 90 patients who received immunotherapy in phase I clinical trials. The data presented in this study may be immediately applicable for medical oncologists as a way to risk-stratify patients who are beginning treatment with immunotherapy.
| S-EPMC7066707 | biostudies-literature
Project description:BackgroundSynthetic colloids are often used during fluid resuscitation and affect coagulation.ObjectiveTo compare the effects of an isotonic crystalloid and synthetic colloid on coagulation in healthy dogs and dogs with systemic inflammation.AnimalsSixteen adult purpose-bred Beagles.MethodsRandomized, placebo-controlled, blinded study. Dogs were randomized into one of two groups receiving fluid resuscitation with either 40 mL/kg IV 0.9% NaCl or tetrastarch after administration of lipopolysaccharide or an equal volume of placebo. After a 14-day washout period, the study was repeated such that dogs received the opposite treatment (LPS or placebo) but the same resuscitation fluid. Blood samples were collected at 0, 1, 2, 4, and 24 hours for measurement of coagulation variables.ResultsAdministration of either fluid to healthy dogs and dogs with systemic inflammation resulted in similar increases in prothrombin time and activated clotting time. In comparison to saline administration, tetrastarch administration resulted in significantly decreased R (P = .017) in healthy dogs, as well as significantly increased activated partial thromboplastin time (P ≤ .016), CL30% (P ≤ .016), and K (P < .001) and significantly decreased platelet count (P = .019), α (P ≤ .001), MA (P < .001), and von Willebrand factor antigen (P < .001) and collagen binding activity (P ≤ .003) in both healthy dogs and dogs with systemic inflammation.Conclusions and clinical importanceTetrastarch bolus administration to dogs with systemic inflammation resulted in a transient hypocoagulability characterized by a prolonged activated partial thromboplastin time, decreased clot formation speed and clot strength, and acquired type 1 von Willebrand disease.
| S-EPMC4858093 | biostudies-literature
Project description:AimsWe investigated whether addition of diastolic dysfunction (DD) and longitudinal strain (LS) to Stage B heart failure (SBHF) criteria (structural or systolic abnormality) improves prediction of symptomatic HF in participants of the SCReening Evaluation of the Evolution of New Heart Failure study, a self-selected population at increased cardiovascular disease risk recruited from members of a health insurance fund in Melbourne and Shepparton, Australia. Both American Society of Echocardiography and European Association of Cardiovascular Imaging (ASE/EACVI) criteria and age-specific Atherosclerosis Risk in Communities (ARIC) study criteria, for SBHF and DD, and ARIC criteria for abnormal LS, were examined.Methods and resultsInclusion criteria were age ≥60 years with one or more of self-reported ischaemic or other heart disease, irregular or rapid heart rhythm, cerebrovascular disease, renal impairment, or treatment for hypertension or diabetes for ≥2 years. Exclusion criteria were known HF, or ejection fraction <50% or >mild valve abnormality detected on previous echocardiography or other imaging. Echocardiography was performed in 3190 participants who were followed for a median of 3.9 (interquartile range: 3.4, 4.5) years after echocardiography. Symptomatic HF was diagnosed in 139 participants at a median of 3.1 (interquartile range: 2.1, 3.9) years after echocardiography. ARIC structural, systolic, and diastolic abnormalities predicted HF in univariate and multivariable proportional hazards analyses, whereas ASE/EACVI structural and systolic, but not diastolic, abnormalities predicted HF. ARIC and ASE/EACVI SBHF criteria predicted HF with sensitivities of 81% and 55%, specificities of 39% and 76%, and C statistics of 0.60 (95% confidence interval: 0.57, 0.64) and 0.66 (0.61, 0.71), respectively. Adding ARIC DD to SBHF increased sensitivity to 94% with specificity of 24% and C statistic of 0.59 (0.57, 0.61), whereas addition of ASE/EACVI DD to SBHF increased sensitivity to 97% but reduced specificity to 9% and the C statistic to 0.52 (0.50, 0.54, P < 0.0001). Addition of LS to ARIC or ASE/EACVI SBHF criteria had minimal impact on prediction of HF.ConclusionsAge-specific ARIC DD criteria, but not ASE/EACVI DD criteria, predicted symptomatic HF, and addition of age-specific ARIC DD criteria to ARIC SBHF criteria improved prediction of symptomatic HF in asymptomatic individuals with cardiovascular disease risk factors. Addition of LS to ASE/EACVI or ARIC SBHF criteria did not improve prediction of symptomatic HF.
| S-EPMC6676278 | biostudies-literature
Project description:AimsThe prevalence of advanced heart failure (HF) is increasing due to the growing number of patients with HF and their better treatment and survival. There is a scarcity of data on the accuracy of HF web-based risk scores in this selected population. This study aimed to assess mortality prediction performance of the Meta-Analysis Global Group in Chronic HF (MAGGIC-HF) risk score and the model of the Barcelona Bio-HF Risk Calculator (BCN-Bio-HF) containing N terminal pro brain natriuretic peptide in HF patients receiving intermittent inotropic support with levosimendan as destination therapy.Methods and resultsFour hundred and three advanced HF patients from 23 tertiary hospitals in Spain receiving intermittent inotropic support with levosimendan as destination therapy were included. Discrimination for all-cause mortality was compared by area under the curve (AUC) and Harrell's C-statistic at 1 year. Calibration was assessed by calibration plots comparing observed versus expected events based on estimated risk by each calculator. The included patients were predominantly men, aged 71.5 [interquartile range 64-78] years, with reduced left ventricular ejection fraction (27.5 ± 9.4%); ischaemic heart disease was the most prevalent aetiology (52.5%). Death rate at 1 year was 26.8%, while the predicted 1-year mortality by BCN-Bio-HF and MAGGIC-HF was 17.0% and 22.1%, respectively. BCN-Bio-HF AUC was 0.66 (Harrell's C-statistic 0.64), and MAGGIC-HF AUC was 0.62 (Harrell's C-statistic 0.61).ConclusionsThe two evaluated risk scores showed suboptimal discrimination and calibration with an underestimation of risk in advanced HF patients receiving levosimendan as destination therapy. There is a need for specific scores for advanced HF.
| S-EPMC10567651 | biostudies-literature