Epidemiological studies show maternal nitrogen dioxide (NO2) exposure associates with congenital heart disease (CHD) risk, but subtypes and mechanisms unclear. Here, we first conducted a systematic review and meta-analysis, which confirmed that prenatal NO₂ exposure significantly increased the risk of coarctation of the aorta (COA) (OR = 1.15, 95% CI: 1.04-1.26). Using a mouse model of prenatal NO₂ exposure, we demonstrated that prenatal NO2 exposure adversely affected fetal cardiac structure and function at embryonic day 18.5, characterized by ventricular dilation, myocardial wall thinning, systolic dysfunction, and cardiac fibrosis predominantly localized to the outflow tract and major vascular roots. Transcriptional profiling of fetal hearts revealed significant enrichment of T cell differentiation pathways, including Th1, Th2, and Th17 cell differentiation. Immunofluorescence analysis further confirmed the imbalance of CD4⁺ T cell subsets, specifically reduced Th1/Th2 and Th17/Treg ratios (key mediators of the above fibrotic phenotype). Importantly, placental proteomics showed activated immune responses and upregulated pro-inflammatory cytokines (TNF-α, IL-1β, IL-6, and IL-17) in fetal circulation, disrupting fetal cardiac CD4+ T-cell homeostasis and inducing fibrosis. Together, these findings identify a "maternal-placental-fetal cardiac immune regulation axis" as critical in NO₂-induced CHD, offering a comprehensive framework for policymakers and clinicians to mitigate CHD burden in polluted areas.

Multiple organ dysfunction syndrome (MODS) is a clinical syndrome characterized by the simultaneous or sequential dysfunction of two or more organs. This condition can result in prolonged hospital stays, high in-hospital mortality rates, and an increased financial burden. Therefore, the identification of risk factors for death is crucial because timely intervention can enhance patient prognosis and reduce mortality rates. This study aimed to investigate the relationship between the Braden Score and in-ICU mortality in patients with MODS. This retrospective study analyzed patients with MODS from the MIMIC-III and MIMIC-IV databases. A multiple-variable logistic model was used to investigate the relationship between initial admission Braden Score and all-cause ICU mortality. The study included 37,981 patients with MODS, with a median age of 68 years (60% male). The in-ICU mortality rate was 8.6%. Upon admission, the Braden score showed a negative association with the mortality which remained consistent even after multivariate adjustment (adjusted OR = 0.87, 95% CI 0.85-0.88, P < 0.0001). This study discovered a significant negative correlation between Braden Score and in-ICU mortality in patients with MODS.

Coronary artery disease (CAD) is the leading cause of death worldwide. A-kinase anchoring protein 1 (AKAP1), thought to regulate the function and structure of mitochondria, is enriched in the heart, where it plays a protective role. However, data on the serum AKAP1 concentration levels in patients with CAD are currently lacking. To address this, the serum levels of AKAP1 in patients with CAD were quantified and their predictive ability for CAD was evaluated in this study. A total of 255 patients referred for coronary angiography were included in this study and classified into two groups (CAD and non-CAD group). A comparative analysis of clinical data and serum AKAP1 concentration levels was performed between the two groups. The patients were then divided into quartiles according to AKAP1 levels. A multivariate logistic regression model was used to assess the independent association of AKAP1 with CAD. The CAD group showed a lower AKAP1 concentration than the non-CAD group (P < 0.01). The AKAP1 level was correlated with a history of CAD (P < 0.001). The receiver operator characteristic (ROC) curve analysis showed a low ability of AKAP1 in predicting CAD (area under the ROC curve = 0.649). Finally, in the multivariate logistic regression model with the highest quartile as the reference, the lowest quartile of AKAP1 remained significantly associated with an increased risk for CAD (odds ratio (OR) = 5.677, 95

p53 is a critical tumor suppressor, and the disruption of its normal function is often a prerequisite for the development or progression of tumors. Our previous works revealed that multiple members of Kr & uuml;ppel-associated box (KRAB) domain zinc-finger proteins (KZFPs) family regulate p53 transcriptional activity by interacting with it. But the tumor biology functions of these members have not been fully elucidated. Here, the pan-cancer analysis related to gastrointestinal cancers (GICs) revealed that ZNF8, a p53-interacting protein, is an unfavorable prognostic factor for patients with malignancies. ZNF8 interacts with p53 and further depresses its transcriptional activity in colon cancer cells. The knockdown of ZNF8 or the overexpression of ZNF8 inhibits or facilitates the in vitro colony formation, migration, invasion, and angiogenesis of p53+/+ +/+ colon cancer HCT116 cells, HepG2 cells and EC109 cells rather than p53-- /- colon cancer HCT116 cells and p53-knockout HepG2 cells, respectively. Xenograft experiments conducted in vivo also showed that the knockdown of ZNF8 in p53+/+ +/+ but not in p53-- /- HCT116 cells curbs the tumor growth and metastasis to lung, leading to an extended life span for tumor-bearing mice. Clinically, two independent immunohistochemistry cohorts of colon cancer and esophageal cancer also indicated that ZNF8 is higher expression in carcinoma tissues than adjacent tissues and this is associated with worse overall survival outcomes in patients without harboring p53 mutation. Together, our results provide insight into the p53-specific tumor oncogenic function of ZNF8. ZNF8 may prove to be a potential target for GICs treatment.

Most deaths in breast cancer patients are attributed to metastasis, and lung metastasis is associated with a particularly poor prognosis; therefore it is imperative to identify potential target for intervention. The transforming growth factor-β (TGF-β) pathway plays a vital role in breast cancer metastasis, in which Smad3 is the key mediator and performs specific functions by binding with different cofactors. However, Smad3 cofactors involved in lung metastasis have not yet been identified. This study first establishes the interactome of Smad3 in breast cancer cells and identifies ZNF8 as a novel Smad3 cofactor. Furthermore, the results reveal that ZNF8 is closely associated with breast cancer lung metastasis prognosis, and specifically facilitates TGF-β pathway-mediated breast cancer lung metastasis by participating in multiple processes. Mechanistically, ZNF8 binds with Smad3 to enhance the H3K4me3 modification and promote the expression of lung metastasis signature genes by recruiting SMYD3. SMYD3 inhibition by BCI121 effectively prevents ZNF8-mediated lung metastasis. Overall, the study identifies a novel cofactor of TGF-β/Smad3 that promotes lung metastasis in breast cancer and introduces potential therapeutic strategies for the early management of breast cancer lung metastasis.

Recent research has revealed that alterations of the gut microbiome (GM) play a comprehensive role in the pathophysiology of HF. However, findings in this field remain controversial. In this study, we focus on differences in GM diversity and abundance between HF patients and non-HF people, based on previous 16S ribosomal RNA (16rRNA) gene sequencing. Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, we conducted a comprehensive search of PubMed, Web of Science, Embase, Cochrane Library, and Ovid databases using the keyword "Heart failure" and "Gastrointestinal Microbiome". A significant decrease in alpha diversity was observed in the HF patients (Chao1, I2= 87.5%, p<0.001; Shannon index, I2=62.8%, p=0.021). At the phylum level, the HF group exhibited higher abundances of Proteobacteria (I2=92.0%, p=0.004) and Actinobacteria (I2=82.5%, p =0.010) , while Bacteroidetes(I2=45.1%, p=0.017) and F/B ratio (I2=0.0%, p<0.001) were lower. The Firmicutes showed a decreasing trend but did not reach statistical significance (I2=82.3%, p=0.127). At the genus level, the relative abundances of Streptococcus, Bacteroides, Alistipes, Bifidobacterium, Escherichia-Shigella, Enterococcus and Klebsiella were increased in the HF group, whereas Ruminococcus, Faecalibacterium, Dorea and Megamona exhibited decreased relative abundances. Dialister, Blautia and Prevotella showed decreasing trends but without statistical significance. This observational meta-analysis suggests that GM changes are associated with HF, manifesting as alterations in GM abundance, disruptions in the production of short-chain fatty acids (SCFAs) bacteria, and an increase in trimethylamine N-oxide (TMAO) producing bacteria.

Abstract Background Epigenetic modifier gene mutations (EMM) have been reported to be associated with poor prognosis in acute myeloid leukemia (AML). Whether allogeneic stem cell transplantation (allo-HSCT) can improve outcomes in this patients remains unknown.Material/Methods: This study retrospectively collected clinical information of 353 AML patients with gene mutations detected by next-generation sequencing (NGS) and analyzed the therapeutic effect of allogeneic stem cell transplantation in acute myeloid leukemia patients with epigenetic modifier gene mutations.Results EMM-positive patients tended to have inferior OS compared with EMM-negative patients (p = 0.065, HR = 1.343, 95%CI: 0.981–1.838), EMM-positive patients had inferior LFS (p = 0.031, HR = 1.385, 95%CI: 1.030–1.863). In EMM-positive patients, multivariate analysis showed that patients who received allo-HSCT had a superior OS (yes vs. no, p < 0.001, HR = 0.213, 95%CI: 0.134–0.339, Table 3) and LFS (yes vs. no, p < 0.001, HR = 0.303, 95%CI: 0.199–0.461, Table 3) compared with patients who did not receive allo-HSCT. A total of 220 patients received allo-HSCT in all patients. Univariate analysis in patients undergoing allo-HSCT showed that EMM was not a risk factor for OS (EMM-positive vs. EMM-negative, p = 0.470, HR = 1.192, 95%CI: 0.740–1.920) and LFS (EMM-positive vs. EMM-negative, p = 0.323, HR = 1.235, 95%CI: 0.813–1.876).Conclusion EMM tended to be a poor risk factor for OS and was a poor risk factor for LFS in our cohort. Allo-HSCT might improve the OS and LFS of EMM-positive patients.

Patients with acute heart failure (AHF) often experience dyspnea, and monitoring and quantifying their breathing patterns can provide reference information for disease and prognosis assessment. In this study, 39 AHF patients and 24 healthy subjects were included. Nighttime chest-abdominal respiratory signals were collected using wearable devices, and the differences in nocturnal breathing patterns between the two groups were quantitatively analyzed. Compared with the healthy group, the AHF group showed a higher mean breathing rate (BR_mean) [(21.03 ± 3.84) beat/min vs. (15.95 ± 3.08) beat/min, P < 0.001], and larger R_RSBI_cv [70.96% (54.34%-104.28)% vs. 58.48% (45.34%-65.95)%, P = 0.005], greater AB_ratio_cv [(22.52 ± 7.14)% vs. (17.10 ± 6.83)%, P = 0.004], and smaller SampEn (0.67 ± 0.37 vs. 1.01 ± 0.29, P < 0.001). Additionally, the mean inspiratory time (TI_mean) and expiration time (TE_mean) were shorter, TI_cv and TE_cv were greater. Furthermore, the LBI_cv was greater, while SD1 and SD2 on the Poincare plot were larger in the AHF group, all of which showed statistically significant differences. Logistic regression calibration revealed that the TI_mean reduction was a risk factor for AHF. The BR_ mean demonstrated the strongest ability to distinguish between the two groups, with an area under the curve (AUC) of 0.846. Parameters such as breathing period, amplitude, coordination, and nonlinear parameters effectively quantify abnormal breathing patterns in AHF patients. Specifically, the reduction in TI_mean serves as a risk factor for AHF, while the BR_mean distinguishes between the two groups. These findings have the potential to provide new information for the assessment of AHF patients.

Introduction Elevated serum uric acid (SUA) levels have been associated with poor outcome in patients with heart failure (HF). Uric acid is associated with inflammation and microvascular dysfunction, which may differentially affect left ventricular ejection fraction (EF) phenotypes. We aimed to identify the role of SUA across EF phenotypes in hospitalized elderly patients with chronic HF. Methods We analyzed 1355 elderly patients who were diagnosed with chronic HF. All patients had SUA levels measured within the first 24 h following admission. Patients with left ventricle EF were categorized as having HF with reduced EF (HFrEF, EF < 40%), HF with mid-range EF (HFmrEF, 40%≦LVEF ≦ 49%) or HF with preserved EF (HFpEF, LVEF ≥ 50%). Endpoints were cardiovascular death, HF rehospitalization, and their composite. The median follow-up period was 18 months. Results Compared with the lowest SUA quartile, the highest SUA quartile was significantly associated with the endpoints (adjusted HR: 2.404, 95% CI: 1.178–4.906, P = 0.016; HR: 1.418, 95% CI: 1.021–1.971, P = 0.037; HR: 1.439, 95% CI: 1.049–1.972, P = 0.024, respectively). After model adjustment, a significant association of SUA with cardiovascular death and the composite endpoint persisted among HFrEF and HFmrEF patients in the highest SUA quartile (P < 0.05 for all). Conclusions In hospitalized elderly patients with chronic HF, SUA is an independent predictor of adverse outcomes, which can be seen in HFrEF and HFmrEF patients.

OBJECTIVE:To investigate the clinical features of transplant-associated thrombotic microangiopathy (TA-TMA) and the prognostic value of different prognostic risk models for TA-TMA.METHODS:The clinical characteristics of 32 TA-TMA patients diagnosed at the First Medical Center of the PLA General Hospital from January 2018 to February 2022 in terms of short-term prognosis and influencing factors were retrospectively analyzed. In addition, the risk population composition ratio, treatment response, and overall survival between the BATAP risk model and the TMA index model were compared, as well as the efficacy of two prognostic risk models for predicting death in patients with TA-TMA.RESULTS:Independent risk factors affecting the short-term prognosis of TA-TMA include III-IV aGVHD prior to TA-TMA diagnosis (P=0.001), renal or neurological dysfunction (P=0.006), and Hb<70 g/L (P=0.043). In the TMA index model, treatment response was worst in the high-risk group (P=0.008), while there was no significant difference in treatment response between different risk groups in the BATAP model (P=0.105). In the BATAP model, there was a statistically significant difference in the OS between the three groups of low risk, intermediate risk, and high risk (87.5% vs 61.1% vs 16.7%, χ2＝6.7, P=0.014). In the TMA index model, there was a statistically significant difference in the OS between the three groups of low risk, intermediate risk, and high risk (77.8% vs 45.5% vs 0.0%, χ2＝7.3, P=0.017). The area under the ROC curve (AUC) of the TMA index model was 0.745 (95%CI: 0.56-0.88, P<0.05), and the AUC of the BATAP model was 0.743 (95%CI: 0.56-0.88, P<0.05), indicating that both prognostic risk models have good predictive value.CONCLUSION:The short-term prognosis of TA-TMA patients might be accurately determined using both the BATAP model and the TMA index model. When predicting the efficacy of TA-TMA in different risk groups, the TMA index model may perform better than the BATAP model.

OBJECTIVE:To analyze the kinetic characteristics of lymphocyte subsets and myeloid-derived suppressor cell (MDSC) in patients who newly diagnosed intermediate- to high-risk aGVHD and treated with steroids-ruxolitinib as the first line therapy from a single-arm, open clinical trial (NCT04061876).METHODS:We prospectively observed the efficacy of 23 patients having intermediate- to high-risk aGVHD and treated with steroids-ruxolitinib as the first line therapy. The kinetic characteristics of lymphocyte subsets and MDSC were monitored, and then we compared them in steroids-ruxolitinib group (n=23), free-aGVHD group (n=20) and steroids group (n=23).RESULTS:Of the 23 patients, the CR rate was 78.26% (18/23) on day 28 after first-line treatment with steroids-ruxolitinib. On day 28 after treatment, patients had lower level of CD4+CD29+ T cells (P=0.08) than that of pre-treatment, whereas levels of other lymphocyte subsets in this study were higher than that of pre-treatment; CD4+CD29+ T cells in CR patients decreased, compared with refractory aGVHD patients. On day 28 of treatment, CD8+CD28- T cells (P=0.03) significantly increased in patients with aGVHD than that in patients without aGVHD, so did CD8+CD28- T / CD8+CD28+ T cell ratio (P=0.03). Compared with patients without aGVHD, patients with aGVHD had lower level of G-MDSC, especially on day 14 after allo-HSCT (P=0.04). Compared with pre-treatment, M-MDSC was higher in CR patients on day 3 and 7 post-treatment (P3=0.01, P7=0.03), e-MDSC was higher on day 28 post-treatment (P=0.01). Moreover, compared with CR patients, M-MDSC was lower in refractory aGVHD patients on day 3 post-treatment (P=0.01) and e-MDSC was lower on day 28 post-treatment (P=0.01). Compared with steroids group, MDSC in steroids-ruxolitinib group was higher, with the most significant difference in M-MDSC (P3=0.0351; P7=0.0142; P14=0.0369).CONCLUSION:We found that patients newly diagnosed intermediate- to high-risk aGVHD receiving first-line therapy with steroids-ruxolitinib achieved high response rate. Moreover, the novel first-line therapy has a small impact on the immune reconstitution of patients after allo-HSCT. Elevated MDSC might predict a better response in aGVHD patients receiving this novel first-line therapy. M-MDSC responded earlier to steroids-ruxolitinib than e-MDSC, G-MDSC.

BACKGROUND With the addition of anti-thymocyte globulin (ATG) to GVHD prophylaxis in patients undergoing transplantation of peripheral blood stem cells (PBSCT), the incidence of cGVHD decreases. However, the optimal dose and timing of ATG remain undetermined. MATERIAL AND METHODS In this historical controlled trial, data from 85 patients who had hematological malignancies and underwent matched sibling donor (MSD)-PBSCT were used to analyze the effectiveness of rabbit ATG (rATG) for prophylaxis of GVHD. Forty patients received 5 mg/kg rATG used for days -5 to -2, and 45 patients did not receive ATG. RESULTS All patients had successful engraftment except for 2 in the non-ATG group, who had platelet engraftment failure. The 2-year cumulative incidence of chronic GVHD (cGVHD) in the ATG group versus non-ATG group was 19.3% (95% CI, 8.4-33.6%) versus 61.4% (95% CI, 45.4-73.9%) (P<0.001), and in those with moderate to severe cGVHD it was 11.0% (95% CI, 3.4-23.6%) versus 31.8% (95% CI, 18.8-45.6%) (P=0.029), respectively. The 2-year cumulative incidence of non-relapse mortality and relapse (CIR) were 0% versus 15.5% (95% CI, 6.8-27.5%) (P=0.018), and 53.3% (95% CI, 35.6-68.1%) versus 26.7% (95% CI, 14.9-40.0%) (P=0.019), respectively. No differences were found in other survival outcomes. In the multivariate analysis, ATG was an independent protective factor for moderate to severe cGVHD (HR=0.314, 95% CI, 0.103-0.958, P=0.042), and was an independent poor risk factor for CIR (HR=2.337, 95% CI, 1.133-4.822, P=0.022). CONCLUSIONS ATG in our strategy was effective for prophylaxis of cGVHD, whereas the relapse rate was increased in patients with rATG.

目的 分析D-二聚体对老年射血分数减低的心力衰竭(heart failure with reduced ejection fraction,HFrEF)住院患者的预后价值.方法 收集2011年1月～2014年1月在解放军总医院心内科住院的老年HFrEF患者714例,依据D-二聚体的临界值分为高水平组224例(D-二聚体＞885 μg/L)和低水平组490例(D-二聚体≤885 μg/L),用ROC曲线分析评估D-二聚体预测不良预后的价值,用Kaplan-Meier曲线分析2组全因死亡差异,用Cox风险比例模型分析影响预后的因素.结果 ROC曲线分析显示,D-二聚体预测全因死亡的曲线下面积为0.632(95％CI:0.559～0.705,P＜0.01),取D-二聚体885 μg/L为临界值时,其特异性为74.7％,敏感性为52.7％.Kaplan-Meier曲线显示,高水平组全因死亡率发生显著高于低水平组(18.8％vs7.3％,Plog rank＜0.01).高D-二聚体(HR=2.144,95％CI:1.311～3.508,P=0.002)与随访期间全因死亡发生率升高独立相关.结论 老年HFrEF住院患者D-二聚体升高与不良预后独立相关.

BACKGROUND:Elevated D-dimer levels have been associated with poor outcomes in patients with cardiovascular disease. AIM:To study this association in elderly patients with chronic heart failure (CHF). METHODS:We analysed 1355 elderly patients who were admitted with CHF. All patients had D-dimer levels measured within the first 24 h following admission. A multivariate logistic regression model was used to assess the variables associated with chronic kidney disease. We used Cox regression analysis to assess the multivariable relationship between the D-dimer and subsequent all-cause death. RESULTS:In the multiple logistic regression analysis, the D-dimer was identified as a risk factor for chronic kidney disease (odds ratio = 1.278, 95% confidence interval 1.138 to 1.436, P < 0.001). The optimal cut-off level for D-dimer to predict all-cause death was found to be >885 ng/mL. In the multivariate Cox proportional-hazards model, a D-dimer level >885 ng/mL remained significantly associated with all-cause death (hazard ratio = 2.003, 95% confidence interval 1.334 to 3.010, P = 0.001). Additional analyses revealed that higher D-dimer levels were associated with an increased risk of all-cause death irrespective of the subtype of heart failure (including heart failure with reduced ejection fraction and heart failure with preserved ejection fraction). CONCLUSION:In elderly patients with CHF, measurement of D-dimer levels may help to risk stratify these patients, and high D-dimer levels might be regarded as a warning sign to intensify therapy.

Mitochondrial damage is involved in the pathogenesis of post-infarction cardiac injury. However, the upstream regulators of mitochondrial damage have not yet been identified. The aim of our study is to explore the role of Sirt3 in post-infarction cardiac injury with a particular focus on mitochondrial fission and AMPK-Drp1 pathways. Our results indicated that Sirt3 was downregulated in the progression of post-infarction cardiac injury. Overexpression of Sirt3 attenuated cardiac fibrosis, sustained myocardial function, inhibited the inflammatory response, and reduced cardiomyocyte death. Functional studies illustrated that chronic post-infarction cardiac injury was characterized by increased mitochondrial fission, which triggered mitochondrial oxidative stress, metabolic disorders, mitochondrial potential reduction and caspase-9 apoptosis in cardiomyocytes. However, Sirt3 overexpression attenuated mitochondrial fission and thus preserved mitochondrial homeostasis and cardiomyocyte viability. Furthermore, our results confirmed that Sirt3 repressed mitochondrial fission via normalizing AMPK-Drp1 pathways. Inhibition of AMPK activity re-activated Drp1 and thus abrogated the inhibitory effect of Sirt3 on mitochondrial fission. Altogether, our results indicate that Sirt3 enhancement could be an effective approach to retard the development of post-infarction cardiac injury via disrupting mitochondrial fission and normalizing the AMPK-Drp1 axis.

BACKGROUND AND PURPOSE:Icariin, a major active ingredient in traditional Chinese medicines, is attracting increasing attention because of its unique pharmacological effects against ischaemic heart disease. The histone deacetylase, sirtuin-1, plays a protective role in ischaemia/reperfusion (I/R) injury, and this study was designed to investigate the protective role of icariin in models of cardiac I/R injury and to elucidate the potential involvement of sirtuin-1. EXPERIMENTAL APPROACH:I/R injury was simulated in vivo (mouse hearts), ex vivo (isolated rat hearts) and in vitro (neonatal rat cardiomyocytes and H9c2 cells). Prior to I/R injury, animals or cells were exposed to icariin, with or without inhibitors of sirtuin-1 (sirtinol and SIRT1 siRNA). KEY RESULTS:In vivo and in vitro, icariin given before I/R significantly improved post-I/R heart contraction and limited the infarct size and leakage of creatine kinase-MB and LDH from the damaged myocardium. Icariin also attenuated I/R-induced mitochondrial oxidative damage, decreasing malondialdehyde content and increasing superoxide dismutase activity and expression of Mn-superoxide dismutase. Icariin significantly improved mitochondrial membrane homeostasis by increasing mitochondrial membrane potential and cytochrome C stabilization, which further inhibited cell apoptosis. Sirtuin-1 was significantly up-regulated in hearts treated with icariin, whereas Ac-FOXO1 was simultaneously down-regulated. Importantly, sirtinol and SIRT1 siRNA either blocked icariin-induced cardioprotection or disrupted icariin-mediated mitochondrial homeostasis. CONCLUSIONS AND IMPLICATIONS:Pretreatment with icariin protected cardiomyocytes from I/R-induced oxidative stress through activation of sirtuin-1 /FOXO1 signalling.

OBJECTIVES:The aim of this study was to develop a clinical risk model that is predictive of in-hospital mortality in elderly patients hospitalized with acute heart failure (AHF).METHODS:2486 patients who were 60 years and older from intensive care units of Cardiology Department in the hospital were analyzed. Independent risk factors for in-hospital mortality were obtained by binary logistic regression and then used to establish the risk prediction score system (RPSS). The area under the curve (AUC) of receiver operator characteristic and C-statistic test were adopted to assess the performance of RPSS and to compare with previous get with the guidelines-heart failure (GWTG-HF).RESULTS:By binary logistic regression analysis, heart rate (OR: 1.043, 95% CI: 1.030-1.057, P < 0.001), left ventricular ejection fraction (OR: 0.918, 95% CI: 0.833-0.966, P < 0.001), pH value (OR: 0.001, 95% CI: 0.000-0.002, P < 0.001), renal dysfunction (OR: 0.120, 95% CI: 0.066-0.220, P < 0.001) and NT-pro BNP (OR: 3.463, 95% CI: 1.870-6.413, P < 0.001) were independent risk factors of in-hospital mortality for elderly AHF patients. Additionally, RPSS, which was composed of all the above-mentioned parameters, provided a better risk prediction than GWTG-THF (AUC: 0.873 vs. 0.818, P = 0.016).CONCLUSIONS:Our risk prediction model, RPSS, provided a good prediction for in-hospital mortality in elderly patients with AHF.

Background The neutrophil-to-lymphocyte (N/L) ratio has been associated with poor prognosis in patients with heart failure, but it has not been compared with N-terminal pro-brain natriuretic peptide (NT-proBNP) in elderly patients with chronic heart failure (CHF). We sought to make this comparison. Methods A total of 1355 elderly patients with CHF were analyzed. A multivariate logistic regression model was used to analyze the variables associated with atrial fibrillation (AF). Cox regression analysis was used to assess the multivariable relationship between the N/L ratio, NT-proBNP level, and subsequent major cardiovascular events (MCE). Results In the multiple logistic regression analysis, the N/L ratio was demonstrated as a risk factor for AF in elderly patients with CHF [odds ratio (OR): 1.079, 95% confidence interval (CI): 1.027-1.134, P = 0.003]. The median follow-up period was 18 months. In a multivariable model using tertiles of both variables, the highest tertile of the N/L ratio was significantly associated with MCE [hazard ratio (HR): 1.407, 95% CI: 1.098-1.802, P = 0.007] compared with the lowest tertile. Similarly, the highest NT-proBNP tertile was also significantly associated with MCE (HR: 1.461, 95% CI: 1.104-1.934, P = 0.008). Conclusions In elderly patients with CHF, the N/L ratio is one of the important risk factors for AF and it is an inexpensive and readily available marker with similar independent prognostic power to NT-proBNP. The risk of MCE increases 1.407-fold when the N/L ratio is elevated to the highest tertile.

We have read with great interest a reader’s letter that addresses several important topics. The first topic concerns inflammatory markers analyzed in study patients. We did not include information on inflammatory markers, such as C-reactive protein (CRP), tumor necrosis factor-α, or interleukin-6, partly because such inflammatory markers are more expensive and difficult to obtain in a clinical practice compared to the neutrophil-to-lymphocyte (N/L) ratio. That lack of information is one of our study’s limitations. To study the relationship between the N/L ratio and CRP level, we added the CRP data. The CRP levels in the total study cohort, in patients who had major cardiovascular events (MCEs) and in patients who did not have MCEs, were (0.387 ± 0.347), (0.443 ± 0.372) and (0.362 ± 0.332) (P < 0.001), respectively. We used the receiver operating characteristic (ROC) curve based on a univariate model to examine the ability of CRP levels to predict MCEs; the area under the curve was 0.564 (P < 0.001, 95% CI: 0.531–0.597). The CRP level and N/L ratio exhibited a positive correlation (r = 0.261, P < 0.001) using the Spearman correlation test. Second, patients with concomitant heart failure (HF) and atrial fibrillation (AF) indeed have a worse prognosis. However, numerous prognostic markers, such as AF, hypertension, smoking, obesity, diabetes, renal impairment, sleep apnea, and coronary artery disease and/or HF hospitalization, have been identified in patients with HF. Although AF was lower in the MCE group in our study, certain prognostic factors with high hazard ratios that we did not include might affect the prognosis of HF when combined with those we did include in the multivariate Cox model. Thus, AF may make the prognosis of HF worse in the multivariate Cox model. In addition, the reader’s observation that New York Heart Association (NYHA) class IV patients are unsuitable for survival studies because of the expectation of a much-shortened lifespan is very relevant. Even though our study had very few NYHA class IV patients (9.1% in the total study cohort and 14.2% in the patients who had MCE), we will focus our attention primarily on NYHA I-II patients in the future. Third, we are sorry to have mistakenly written NYHA as HYHA. We express our sincere apologies for this mistake. Finally, we agree that multicenter randomized trials with large sample sizes and long-term follow-up should be conducted in the future, as larger trials would make our conclusions more reliable. Our investigation is still underway. We hope that more markers, such as the N/L ratio, that are inexpensive and can be readily obtained at the time of admission for every HF patient will be observed and that the relationship between N/L ratio and poor prognosis in HF will be confirmed in more research populations.