The effect of diabetes on the diagnostic and prognostic performance of mid-region pro-atrial natriuretic peptide and mid-region pro-adrenomedullin in patients with acute dyspnea

Serum mid-regional pro-atrial natriuretic peptide (MR-proANP) and pro-adrenomedullin (MR-proADM) are novel biomarkers for acute heart failure (AHF). Like other AFH biomarkers, the performance of these tests are affected by the presence of clinical variables such as renal failure and obesity. In a substudy of the Biomarkers from Acute Heart Failure Study, we show that diabetes did not influence the performance of these markers with regards to AHF diagnosis or 90-day all cause death. However, in patients without AHF, increased MR-proADM alone was associated with the presence of diabetes.     

Concentration of circulating microparticles: a new biomarker of acute heart failure after cardiac surgery with cardiopulmonary bypass

Acute heart failure(AHF) is a severe complication after cardiac surgery with cardiopulmonary bypass(CPB). Although some AHF biomarkers have been used in clinic, they have limitations when applied in the prediction and diagnosis of AHF after cardiac surgery with CPB, and there are still no effective and specific biomarkers. We and other researchers have shown that circulating microparticles(MPs) increased in a variety of cardiovascular diseases. However, whether the concentration of circulating MPs could be a new biomarker for AHF after cardiac surgery remains unknown. Here, 90 patients undergoing cardiac surgery with CPB and 45 healthy subjects were enrolled. Patients were assigned into AHF(n=14) or non-AHF(n=76) group according to the diagnosis criteria of AHF. The concentrations of circulating MPs were determined before, as well as 12 h and 3 days after operation with nanoparticle tracking analysis technique. MPs concentrations in patients before surgery were significantly higher than those of healthy subjects. Plasma levels of MPs were significantly elevated at 12 h after surgery in patients with AHF, but not in those without AHF, and the circulating MPs concentrations at 12 h after surgery were higher in AHF group compared with non-AHF group. Logistic regression analysis indicated that MPs concentration at postoperative 12 h was an independent risk factor for AHF. The area under receiver operating characteristic curve for MPs concentration at postoperative 12 h was 0.87 and the best cut-off value is 5.20×10~8 particles mL~(–1) with a sensitivity of 93% and a specificity of 70%. These data suggested that the concentration of circulating MPs might be a new biomarker for the occurrence of AHF after cardiac surgery with CPB.     

Biomarkers and diagnostics in heart failure

Heart failure (HF) biomarkers have dramatically impacted the way HF patients are evaluated and managed. B-type natriuretic peptide (BNP) and N-terminal proBNP (NT-proBNP) are the gold standard biomarkers in determining the diagnosis and prognosis of HF, and studies on natriuretic peptide-guided HF management look promising. An array of additional biomarkers has emerged, each reflecting different pathophysiological processes in the development and progression of HF: myocardial insult, inflammation and remodeling. Novel biomarkers, such as mid-regional pro atrial natriuretic peptide (MR-proANP), mid-regional pro adrenomedullin (MR-proADM), highly sensitive troponins, soluble ST2 (sST2), growth differentiation factor (GDF)-15 and Galectin-3, show potential in determining prognosis beyond the established natriuretic peptides, but their role in the clinical care of the patient is still partially defined and more studies are needed. This article is part of a Special Issue entitled: Heart failure pathogenesis and emerging diagnostic and therapeutic interventions.     

How should we monitor the cardiovascular benefit of sodium–glucose cotransporter 2 inhibition?

Background

High N-terminal pro-brain-type natriuretic peptide levels have been associated with a lower risk of type 2 diabetes mellitus (T2D). However, less is known about other cardiac stress biomarkers in this context. Here we evaluated the association of mid-regional pro-atrial natriuretic peptide (MR-proANP), C-terminal pro-arginine vasopressin (copeptin), C-terminal pro-endothelin-1 (CT-proET-1) and mid-regional pro-adrenomedullin (MR-proADM) with incident T2D and changes in glucose metabolism.

Methods

We performed a prospective cohort study using data from the population-based KORA F4/FF4 study. 1773 participants (52.3% women) with MR-proANP measurements and 960 (52.7% women) with copeptin, CT-proET-1 and MR-proADM measurements were included. We examined associations of circulating plasma levels of MR-proANP, copeptin, CT-proET-1 and MR-proADM with incident T2D, the combined endpoint of incident prediabetes/T2D and with fasting and 2 h-glucose, fasting insulin, HOMA-IR, HOMA-B and HbA1c at follow-up. Logistic and linear regression models adjusted for age, sex, waist circumference, height, hypertension, total/HDL cholesterol ratio, triglycerides, smoking, physical activity and parental history of diabetes were used to compute effect estimates.

Results

During a median follow-up time of 6.4 years (25th and 75th percentiles: 6.0 and 6.6, respectively), 119 out of the 1773 participants and 72 out of the 960 participants developed T2D. MR-proANP was inversely associated with incident T2D (odds ratio [95% confidence interval]: 0.75 [0.58; 0.96] per 1-SD increase of log MR-proANP). Copeptin was positively associated with incident prediabetes/T2D (1.29 [1.02; 1.63] per 1-SD increase of log copeptin). Elevated levels of CT-proET-1 were associated with increased HOMA-B at follow-up, while elevated MR-proADM levels were associated with increased fasting insulin, HOMA-IR and HOMA-B at follow-up. These associations were independent of previously described diabetes risk factors.

Conclusions

High plasma concentrations of MR-proANP contributed to a lower risk of incident T2D, whereas high plasma concentrations of copeptin were associated with an increased risk of incident prediabetes/T2D. Furthermore, high plasma concentrations of CT-proET-1 and MR-proADM were associated with increased insulin resistance. Our study provides evidence that biomarkers implicated in cardiac stress are associated with incident T2D and changes in glucose metabolism.

     

Biomarker response and therapy prediction in renal denervation therapy – the role of MR-proadrenomedullin in a multicenter approach

Background: Renal denervation has been proposed as a therapeutic option in patients with resistant hypertension. Circulating blood borne biomarkers might be helpful to identify individuals responding to RDN therapy. MR-proADM is a strong prognostic marker in patients with cardiovascular disease. The aim of this multicenter study was to evaluate the effect of RDN on MR-proADM concentrations.

Methods and results: We measured MR-proADM, BNP, and MR-proANP in 110 patients before and after RDN in a multicenter setting. All patients were followed up after 1 and 6 months by office and ambulatory blood pressure (BP) measurements. The mean office BP decreased from 165/89 to 152/87?mmHg 6 months after RDN (systolic: p?<?0.001; diastolic: ns), the responder-rate was 74%. Intriguingly MR-proADM concentrations increased from 0.66 to 0.69?nmol/L (p?<?0.001) and were significantly associated with reduction of systolic office BP after 6 months in multivariate analyses (coefficient ?0.0018, p?<?0.001). In therapy-responders MR-proADM concentrations showed a significantly higher increase over time (coefficient 0.0105, p?<?0.05), as compared to non-responders. There were no significant differences in BP change for individuals with low and high baseline MR-proADM (BP-Delta low MR-proADM ?23/?4?mmHg vs. high MR-proADM ?24/?5?mmHg). The natriuretic biomarkers BNP and MR-proANP did not change significantly after 6 months. Biomarkers at baseline were not able to predict for therapy-responder.

Conclusion: In patients undergoing RDN, baseline measurements of various biomarkers had no prognostic use for therapy success in this short time follow-up period in a multicenter approach. Intriguingly, MR-proADM showed a significant association with BP reduction after 6 months.     

Prognostic Implication of Physical Signs of Congestion in Acute Heart Failure Patients and Its Association with Steady-State Biomarker Levels

Background

Congestive physical findings such as pulmonary rales and third heart sound (S3) are hallmarks of acute heart failure (AHF). However, their role in outcome prediction remains unclear. We sought to investigate the association between congestive physical findings upon admission, steady-state biomarkers at the time of discharge, and long-term outcomes in AHF patients.

Methods

We analyzed the data of 133 consecutive AHF patients with an established diagnosis of ischemic or non-ischemic (dilated or hypertrophic) cardiomyopathy, admitted to a single-center university hospital between 2006 and 2010. The treating physician prospectively recorded major symptoms and congestive physical findings of AHF: paroxysmal nocturnal dyspnea, orthopnea, pulmonary rales, jugular venous distension (JVD), S3, and edema. The primary endpoint was defined as rehospitalization for HF.

Results

Majority (63.9%) of the patients had non-ischemic etiology and, at the time of admission, S3 was seen in 69.9% of the patients, JVD in 54.1%, and pulmonary rales in 43.6%. The mean follow-up period was 726 ± 31days. Patients with pulmonary rales (p < 0.001) and S3 (p  =  0.011) had worse readmission rates than those without these findings; the presence of these findings was also associated with elevated troponin T (TnT) levels at the time of discharge (odds ratio [OR] 2.8; p  =  0.02 and OR 2.6; p  =  0.05, respectively).

Conclusion

Pulmonary rales and S3 were associated with inferior readmission rates and elevated TnT levels on discharge. The worsening of the readmission rate owing to congestive physical findings may be a consequence of on-going myocardial injury.     

Relationship between plasma mid-regional pro-adrenomedullin level and resistance to antihypertensive therapy in stable kidney transplant recipients

We investigated the relationship between plasma mid-regional pro-adrenomedullin (MR-proADM)-like immunoreactive substance (IS) level and clinical characteristics associated with renal failure or resistance to antihypertensive therapy in stable kidney transplant recipients. Forty-six Japanese kidney transplant recipients who underwent transplantation more than 90 days prior to the study were included. To evaluate resistance to antihypertensive therapy, we calculated the treatment intensity score of the antihypertensive drugs in each recipient. Morning blood samples were collected and plasma MR-proADM-IS levels were measured using an enzyme immunoassay. A significant correlation was observed between plasma MR-proADM-IS level with creatinine clearance or treatment intensity score. Multiple regression analysis identified plasma MR-proADM level and body mass index as significant independent factors associated with treatment intensity score. Plasma MR-proADM level may be a useful biomarker indicating the degree of resistance to antihypertensive therapy.     

实时三维超声心动图联合血清NT-proBNP、MR-proADM、sST2对心力衰竭患者诊断及预后的评估价值

摘要 目的：探讨实时三维超声心动图（RT-3DE）联合血清N末端脑钠肽前体（NT-proBNP）、肾上腺髓质素前体中段肽（MR-proADM）、可溶性人基质裂解素2（sST2）对心力衰竭（HF）患者诊断及预后的评估价值。方法：选择2020年3月至2022年10月阳光融和医院收治的112例HF患者（HF组）,另选择同期体检健康的50例志愿者（对照组）。所有受试者均接受RT-3DE检查,同时检测血清NT-proBNP、MR-proADM、sST2水平。对比两组RT-3DE参数和血清NT-proBNP、MR-proADM、sST2水平。HF患者出院后随访6个月,统计患者预后情况;根据预后将患者分为预后不良组（37例）和预后良好组（75例）。受试者工作特征（ROC）曲线分析RT-3DE参数联合血清NT-proBNP、MR-proADM、sST2诊断HF的临床价值及对预后不良的预测价值。结果：HF组左室收缩末期容积（LVESV）、左室舒张末期容积（LVEDV）、左室舒张末期容积指数（LVEDVI）、收缩末期容积指数（LVESVI）、血清NT-proBNP、MR-proADM、sST2水平高于对照组（P＜0.05）,左室射血分数（LVEF）低于对照组（P＜0.05）。RT-3DE参数联合血清NT-proBNP、MR-proADM、sST2诊断HF的曲线下面积（AUC）为0.902,高于各指标单独诊断。预后不良组LVESV、LVEDV、LVEDVI、LVESVI、血清NT-proBNP、MR-proADM、sST2水平高于预后良好组（P＜0.05）,LVEF低于预后良好组（P＜0.05）。RT-3DE参数联合NT-proBNP、MR-proADM、sST2预测HF预后不良的AUC为0.937,高于各指标单独预测。结论：HF患者LVESV、LVEDV、LVEDVI、LVESVI、血清NT-proBNP、MR-proADM、sST2水平增高,LVEF降低,联合RT-3DE参数和血清NT-proBNP、MR-proADM、sST2可提高对HF诊断和预后预测的效能。     

Multiple Biomarkers and Atrial Fibrillation in the General Population

Background

Different biological pathways have been related to atrial fibrillation (AF). Novel biomarkers capturing inflammation, oxidative stress, and neurohumoral activation have not been investigated comprehensively in AF.

Methods and Results

In the population-based Gutenberg Health Study (n = 5000), mean age 56±11 years, 51% males, we measured ten biomarkers representing inflammation (C-reactive protein, fibrinogen), cardiac and vascular function (midregional pro adrenomedullin [MR-proADM], midregional pro atrial natriuretic peptide [MR-proANP], N-terminal pro-B-type natriuretic peptide [Nt-proBNP], sensitive troponin I ultra [TnI ultra], copeptin, and C-terminal pro endothelin-1), and oxidative stress (glutathioneperoxidase-1, myeloperoxidase) in relation to manifest AF (n = 161 cases). Individuals with AF were older, mean age 64.9±8.3, and more often males, 71.4%. In Bonferroni-adjusted multivariable regression analyses strongest associations per standard deviation increase in biomarker concentrations were observed for the natriuretic peptides Nt-proBNP (odds ratio [OR] 2.89, 99.5% confidence interval [CI] 2.14–3.90; P<0.0001), MR-proANP (OR 2.45, 99.5% CI 1.91–3.14; P<0.0001), the vascular function marker MR-proADM (OR 1.54, 99.5% CI 1.20–1.99; P<0.0001), TnI ultra (OR 1.50, 99.5% CI 1.19–1.90; P<0.0001) and. fibrinogen (OR 1.44, 99.5% CI 1.19–1.75; P<0.0001). Based on a model comprising known clinical risk factors for AF, all biomarkers combined resulted in a net reclassification improvement of 0.665 (99.3% CI 0.441–0.888) and an integrated discrimination improvement of >13%.

Conclusions

In conclusion, in our large, population-based study, we identified novel biomarkers reflecting vascular function, MR-proADM, inflammation, and myocardial damage, TnI ultra, as related to AF; the strong association of natriuretic peptides was confirmed. Prospective studies need to examine whether risk prediction of AF can be enhanced beyond clinical risk factors using these biomarkers.     

Distinct roles for renal particulate and soluble guanylyl cyclases in preserving renal function in experimental acute heart failure

Worsening renal function in the setting of human acute heart failure (AHF) predicts poor outcomes, such as rehospitalization and increased mortality. Understanding potential renoprotective mechanisms is warranted. The guanylate cyclase (GC) enzymes and their second messenger cGMP are the target of two important circulating neurohumoral systems with renoprotective properties. Specifically, natriuretic peptides (NP) released from the heart with AHF target particulate GC in the kidney, while the nitric oxide (NO) system is an activator of renal soluble GC. We hypothesized that both systems are essential to preserve renal excretory and hemodynamic function in AHF but with distinct roles. We investigated these roles in three groups of anesthetized dogs (6 each) with AHF induced by rapid ventricular pacing. After a baseline AHF clearance, each group received intrarenal vehicle (control), N(G)-monomethyl-l-arginine (l-NMMA), a competitive NO inhibitor (50 microg.kg(-1).min(-1)) or a specific NP receptor antagonist, HS-142-1 (0.5 mg/kg). We observed that intrarenal l-NMMA decreased renal blood flow (RBF) without significant decreases in glomerular filtration rate (GFR), urinary sodium excretion (UNaV), or urinary cGMP. In contrast, HS-142-1 resulted in a decrease in UNaV and cGMP excretion together with a reduction in GFR and an increase in distal fractional tubular sodium reabsorption. We conclude that in AHF, the NP system plays a role in maintaining sodium excretion and GFR, while the function of NO is in the maintenance of RBF. These studies have both physiological and therapeutic implications warranting further research into cardiorenal interactions in this syndrome of AHF.     

The association of mid-regional pro-adrenomedullin and mid-regional pro-atrial natriuretic peptide with mortality in an incident dialysis cohort

High levels of the plasma peptides mid-regional pro-adrenomedullin (MR-proADM) and mid-regional pro-atrial natriuretic peptide (MR-proANP) are associated with clinical outcomes in the general population. Data in patients with chronic kidney disease are sparse. We therefore investigated the association of MR-proANP and MR-proADM levels with all-cause and cardiovascular (CV) mortality, CV events and peripheral arterial disease in 201 incident dialysis patients of the INVOR-Study prospectively followed for a period of up to more than 7 years. The overall mortality rate was 43%, thereof 43% due to CV events. Both baseline MR-proANP and MR-proADM were associated with higher risk of all-cause (HR = 1.44, p = 0.001 and HR = 1.32, p = 0.002, respectively) and CV mortality (HR = 1.75, p<0.001 and HR = 1.41, p = 0.007, respectively) after adjustment for age, sex, previous CV events, diabetes mellitus and time-dependent type of renal replacement therapy. We then stratified patients in high risk (both peptides in the upper tertile), intermediate risk (only one of the two peptides in the upper tertile) and low risk (none in the upper tertile). Although demographic, clinical and laboratory variables were similar among the intermediate and high risk group, to be with both parameters in the upper tertile was associated with a 3-fold higher risk for all-cause (HR = 2.87, p<0.001) and CV mortality (HR = 3.58, p = 0.001). In summary, among incident dialysis patients MR-proANP and MR-proADM were shown to be associated with all-cause and CV mortality, with the highest risk when both parameters were in the upper tertiles.     

Biomarker dynamics in cardiac surgery: a prospective observational study on MR-proADM,MR-proANP,hs-CRP and sP-selectin plasma levels in the perioperative period

Abstract

Background: For many biomarkers in cardiac surgery, there is a lack of knowledge regarding the normal dynamics of plasma levels during the perioperative course. The aim of this study was to investigate the perioperative dynamics of MR-proADM, MR-proANP, hs-CRP and sP-selectin in cardiac surgery.

Method: A prospective observational pilot study with 20 patients scheduled for open cardiac surgery procedures with cardiopulmonary bypass (CPB). Plasma samples were taken for each patient and biomarker during the pre-, per- and postoperative period until Day 6 postoperatively.

Results: MR-proADM increased significantly from 0.62 [IQR; 0.54–0.93]?nmol/L preoperatively to 1.20 [1.04–1.80]?nmol/L postoperative Day 1. MR-proANP increased significantly from 125 [77–152]?pmol/L preoperatively to 198 [168–307]?pmol/L on weaning from CPB. hs-CRP increased significantly from 2.5?mg/L [0.4–12] preoperatively to peak at 208?mg/L [186–239] postoperative Day 3. The preoperative level of sP-selectin at 23.0 [21.3–26.3]?ng/mL initially fell at weaning from CPB, followed by a significant peak of 25.5 [22.7–27.7]?ng/mL 8?h postoperatively.

Conclusions: The findings in this study may help to understand the physiology of the biomarkers analysed and their response to cardiac surgical trauma including CPB. Furthermore, these findings will guide us in further research on the clinical usefulness of these biomarkers.     

Effects of the Use of Assisted Reproductive Technologies and an Obesogenic Environment on Resistance Artery Function and Diabetes Biomarkers in Mice Offspring

Maternal obesity affects the incidence of cardiovascular disease and diabetes in offspring. Also the use of assisted reproductive technologies (ART) has been associated with cardiovascular deficiencies in offspring. Obese women often suffer from infertility and use ART to achieve a pregnancy, but the combined effects of maternal obesity and ART on cardiovascular health and incidence of diabetes in the offspring is not known. Here, we report the effects of the use of ART within an obesogenic environment, consisting of feeding a western diet (WD) to dams and offspring, on resistance artery function and presence of diabetes biomarkers in juvenile mice offspring. Our results indicate that WD and ART interacted to induce endothelial dysfunction in mesenteric resistance arteries isolated from 7-week-old mice offspring. This was determined by presence of a reduced acetylcholine-induced dilation compared to controls. The arteries from these WD-ART mice also had greater wall cross-sectional areas and wall to lumen ratios indicative of vascular hypertrophic remodeling. Of the diabetes biomarkers measured, only resistin was affected by a WD×ART interaction. Serum resistin was significantly greater in WD-ART offspring compared to controls. Diet and sex effects were observed in other diabetes biomarkers. Our conclusion is that in mice the use of ART within an obesogenic environment interacts to favor the development of endothelial dysfunction in the resistance arteries of juvenile offspring, while having marginal effects on diabetes biomarkers.     

Plasma Midregional Pro-Adrenomedullin Improves Prediction of Functional Outcome in Ischemic Stroke

Background

To evaluate if plasma levels of midregional pro-adrenomedullin (MR-proADM) improve prediction of functional outcome in ischemic stroke.

Methods

In 168 consecutive ischemic stroke patients, plasma levels of MR-proADM were measured within 24 hours from symptom onset. Functional outcome was assessed by the modified Rankin Scale (mRS) at 90 days following stroke. Logistic regression, receiver operating characteristics (ROC) curve analysis, net reclassification improvement (NRI), and Kaplan-Meier survival analysis were applied.

Results

Plasma MR-proADM levels were found significantly higher in patients with unfavourable (mRS 3–6) compared to favourable (mRS 0–2) outcomes. MR-proADM levels were entered into a predictive model including the patients'' age, National Institutes of Health Stroke Scale (NIHSS), and the use of recanalization therapy. The area under the ROC curve did not increase significantly. However, category-free NRI of 0.577 (p<0.001) indicated a significant improvement in reclassification of patients. Furthermore, MR-proADM levels significantly improved reclassification of patients in the prediction of outcome by the Stroke Prognostication using Age and NIHSS-100 (SPAN-100; NRI = 0.175; p = 0.04). Kaplan-Meier survival analysis showed a rising risk of death with increasing MR-proADM quintiles.

Conclusions

Plasma MR-proADM levels improve prediction of functional outcome in ischemic stroke when added to the patients'' age, NIHSS on admission, and the use of recanalization therapy. Levels of MR-proADM in peripheral blood improve reclassification of patients when the SPAN-100 is used to predict the patients'' functional outcome.     

Lack of pro-inflammatory cytokine mobilization predicts poor prognosis in patients with acute heart failure

AimsThe aim of this study was to gain insight in the inflammatory response in acute heart failure (AHF) by assessing (1) plasma cytokine profiles and (2) prognostic value of circulating cytokines in AHF patients.Methods and resultsPlasma levels of 26 cytokines were quantified by multiplex protein arrays in 36 patients with congestive AHF, characterized by echocardiographic, radiologic, and clinical examinations on admission, during hospitalization and at discharge. Recurrent AHF leading to death or readmission constituted the combined end point, and all patients were followed for 120 days after discharge. Levels of 15 of the measured cytokines were higher in AHF than in healthy subjects (n = 22) on admission. Low levels of MCP-1, IL-1β and a low IL-1β/IL-1ra ratio predicted fatal and non-fatal AHF within 120 days. Patients with low circulating levels of IL-1β had lower left ventricular ejection fraction and higher levels of N-terminal pro-B-type natriuretic peptide, while patients with low levels of MCP-1 had higher E/E′ and inferior caval vein diameter, than patients with high levels.ConclusionImmune activation, reflected in increased cytokine levels, is present in AHF patients. Interestingly, failure to increase secretion of IL-1β and MCP-1 during AHF is associated with poor outcome.     

Usefulness of Midregional Proadrenomedullin to Predict Poor Outcome in Patients with Community Acquired Pneumonia

Background

midregional proadrenomedullin (MR-proADM) is a prognostic biomarker in patients with community-acquired pneumonia (CAP). We sought to confirm whether MR-proADM added to Pneumonia Severity Index (PSI) improves the potential prognostic value of PSI alone, and tested to what extent this combination could be useful in predicting poor outcome of patients with CAP in an Emergency Department (ED).

Methods

Consecutive patients diagnosed with CAP were enrolled in this prospective, single-centre, observational study. We analyzed the ability of MR-proADM added to PSI to predict poor outcome using receiver operating characteristic (ROC) curves, logistic regression and risk reclassification and comparing it with the ability of PSI alone. The primary outcome was “poor outcome”, defined as the incidence of an adverse event (ICU admission, hospital readmission, or mortality at 30 days after CAP diagnosis).

Results

226 patients were included; 33 patients (14.6%) reached primary outcome. To predict primary outcome the highest area under curve (AUC) was found for PSI (0.74 [0.64-0.85]), which was not significantly higher than for MR-proADM (AUC 0.72 [0.63-0.81, p > 0.05]). The combination of PSI and MR-proADM failed to improve the predictive potential of PSI alone (AUC 0.75 [0.65-0.85, p=0.56]). Ten patients were appropriately reclassified when the combined PSI and MR-proADM model was used as compared with the model of PSI alone. Net reclassification improvement (NRI) index was statistically significant (7.69%, p = 0.03) with an improvement percentage of 3.03% (p = 0.32) for adverse event, and 4.66% (P = 0.02) for no adverse event.

Conclusion

MR-proADM in combination with PSI may be helpful in individual risk stratification for short-term poor outcome of CAP patients, allowing a better reclassification of patients compared with PSI alone.     

Comparative analysis of gene expression profiles of acute hepatic failure and that of liver regeneration in rat

To explore the relevance of rat liver regeneration (LR) to acute hepatic failure (AHF), Rat Genome 230 2.0 Array was used to detect their gene expression profiles in this study, and the reliability of the detection results was confirmed by real-time-PCR. 1012 genes were found to be significantly changed in AHF occurrence and 948 genes in LR. Hierarchical clustering analysis showed that physiological activities of AHF and those of LR had no time correlation. Hierarchical clustering analysis (which is performed to group genes based on the similarity of expression patterns) showed that physiological activities of AHF and those of LR had no time correlation. K-means clustering analysis (which is used to check the difference in the relevant predictor variables between different groups is significant or not) demonstrated that gene expression trend of C1 group (genes relate to categories of stimulus–response and cell apoptosis, etc.) in AHF and in LR was extremely similar, that those of their C2 group (categories of regulation of homeostasis and hormone stimulation, etc.) were contrary, and that those of their C3 (material and energy metabolism and oxidation reduction, etc.), C4 (Cell cycle-related genes) and C5 (cell proliferation-related genes) groups were also similar with the gene expression changes of LR more abundant. GO classifications and functional clustering analysis (which was used to statistics the numbers or composition of proteins or genes at a function level) revealed that cellular processes including immune response, inflammatory reaction, cell migration and adhesion, etc. were increased both in AHF and in LR, whereas material and energy metabolism were decreased. Of them, stimulus response, inflammatory reaction and regulation of apoptosis, etc. were stronger in AHF occurrence than in LR, but ion homeostasis, hormonal response, regulation of cell division and proliferation, etc. were weaker in AHF occurrence. Gene expression changes and physiological activities of AHF and those of LR not only have similarities but also differences.     

Circulating microRNAs and Outcome in Patients with Acute Heart Failure

Background

The biomarker value of circulating microRNAs (miRNAs) has been extensively addressed in patients with acute coronary syndrome. However, prognostic performances of miRNAs in patients with acute heart failure (AHF) has received less attention.

Methods

A test cohort of 294 patients with acute dyspnea (236 AHF and 58 non-AHF) and 44 patients with stable chronic heart failure (CHF), and an independent validation cohort of 711 AHF patients, were used. Admission levels of miR-1/-21/-23/-126/-423-5p were assessed in plasma samples.

Results

In the test cohort, admission levels of miR-1 were lower in AHF and stable CHF patients compared to non-AHF patients (p = 0.0016). Levels of miR-126 and miR-423-5p were lower in AHF and in non-AHF patients compared to stable CHF patients (both p<0.001). Interestingly, admission levels of miR-423-5p were lower in patients who were re-admitted to the hospital in the year following the index hospitalization compared to patients who were not (p = 0.0001). Adjusted odds ratio [95% confidence interval] for one-year readmission was 0.70 [0.53–0.93] for miR-423-5p (p = 0.01). In the validation cohort, admission levels of miR-423-5p predicted 1-year mortality with an adjusted odds ratio [95% confidence interval] of 0.54 [0.36–0.82], p = 0.004. Patients within the lowest quartile of miR-423-5p were at high risk of long-term mortality (p = 0.02).

Conclusions

In AHF patients, low circulating levels of miR-423-5p at presentation are associated with a poor long-term outcome. This study supports the value of miR-423-5p as a prognostic biomarker of AHF.     

实验性急性肝衰竭大鼠血清中TNF-α的来源及水平变化

目的研究D-氨基半乳糖／内毒素所致大鼠急性肝衰竭模型中血清内TNF-α的来源及不同时间点的水平变化。方法取30只Wistar大鼠腹腔内注射D-氨基半乳糖／内毒素诱导大鼠急性肝衰竭模型（AHF组,n=30）,于建模3h、6h、12h、24h、48h、72h各取5只动物检测其血清丙氨酸转氨酶（ALT）与肝组织的病理形态学变化;采用ELISA检测不同时间点动物血清中TNF-α水平的变化;通过免疫组化法检测不同时间点动物肝、肺组织内TNF-α的表达。另取30只Wistar大鼠腹腔内注射等量生理盐水为正常对照（N组,n=30）。结果AHF组各时间点血清ALT的增高与N组相比有统计学差异（P〈0．05）,肝脏内炎细胞浸润、坏死明显;AHF组与N组相比血清内TNF-α的增高在3h（P〈0．01）、6h（P〈0．05）有统计学差异;AHF组肺组织与N组相比TNF-α的表达在3h、6h、12h（均为P〈0．01）有统计学差异。结论本实验成功建立了大鼠AHF模型;TNF-α在此模型的早期阶段起重要作用;肺脏可能是血清内TNF-α的主要来源之一。