Background Red blood cell distribution width (RDW) and N‐terminal pro brain natriuretic peptide (NT‐proBNP) may predict the prognosis of heart failure (HF). However, the impact of combined RDW and NT‐proBNP levels as a prognostic marker of HF remains unclear and the significance of this combination at various time‐points has not been sufficiently studied. Hypothesis RDW can predict prognosis in HF at various time‐points and combination with NT‐proBNP improves the prognostic value. Methods Patients admitted to HF care unit of Fuwai Hospital CAMS&PUMC (Beijing, China) with a diagnosis of HF from November 2008 to November 2018 were analyzed retrospectively. Results In total, 3231 patients with available RDW data at admission were evaluated (median age 58 years, 71.9% males, 39.7% coronary heart disease, 68.6% New York Heart Association [NYHA] III or IV). Median RDW and NT‐proBNP at admission were 13.4% (interquartile range [IQR]: 12.7%–14.5%), and 1723.00 pg/ml (IQR: 754.00–4006.25 pg/ml), respectively. During 2.9‐year median follow‐up, all‐cause death occurred in 1075 (33.27%) patients. Kaplan–Meier survival curve and Cox proportional‐hazard models, showed patients in the top quarter RDW had a 32.0% increased mortality compared to the bottom quarter (hazard ratio: 4.39, 95% confidence interval: 3.59–5.38; p <.001). The top quarter RDW retained independent prognostic value across HF with reduced ejection fraction [HFrEF], HF with mid‐range ejection fraction [HFmrEF], and HF with preserved ejection fraction [HFpEF] subgroups. Patients were subsequently divided into four groups by median RDW and NT‐proBNP. Comparison of Kaplan–Meier survival curves for various groups showed good risk stratification ( p < .001). Conclusions RDW is an independent predictor of mortality among patients with HF in the short‐, medium‐, and long‐term. Combination of RDW and NT‐proBNP improves the prognostic value. This is true across all clinical subtypes of heart failure (HFrEF, HFmrEF, HFpEF), and among most subgroups of patients with various comorbidities (infection, diabetes, hypertension).
Aims Mildly dilated cardiomyopathy (MDCM) was characterized as a subset of dilated cardiomyopathy (DCM) with systolic dysfunction and modest ventricular dilatation, of which the prognostic studies were limited. We aimed to compare the prognostic value of the N-terminal pro-brain natriuretic peptide (NT-proBNP) and high-sensitivity C-reactive protein (hs-CRP) between MDCM and DCM. Methods and resultsWe retrospectively included hospitalized patients diagnosed with DCM and a left ventricular ejection fraction ≤ 50% at Fuwai Hospital from 2006 to 2017. MDCM was defined as left ventricular end-diastolic diameter index (LVEDDi) ≤ 33 mm/m 2 in males and ≤34 mm/m 2 in females. A total of 640 patients (median age 49 years, 24.8% female) were included in this study. At baseline, 110 cases (17%) were categorized as MDCM and 529 cases (83%) as DCM. Of 282 patients who had follow-up echocardiograms ≥ 6 months, 7 MDCM patients (11.1%) evolved to DCM and 70 DCM patients (32.0%) recovered to MDCM by the change of LVEDDi. Compared with DCM, patients with baseline MDCM had lower composite risks of all-cause mortality, heart transplantation, and heart failure rehospitalization [adjusted hazard ratio (HR) 0.63, 95% confidence interval (CI) 0.43-0.93, P = 0.019]. Both hs-CRP and NT-proBNP were independently associated with the composite endpoint in the overall cohort (hs-CRP: adjusted HR 1.07, 95% CI 1.00-1.15, P = 0.036; NT-proBNP: adjusted HR 1.11, 95% CI 1.02-1.22, P = 0.019). After a propensity-score matching between MDCM and DCM, higher NT-proBNP (above the median) was significantly associated with the outcome in DCM patients (HR 1.83, 95% CI 1.05-3.20, P = 0.034), but not in MDCM patients (HR 1.54, 95% CI 0.76-3.11, P = 0.227). On the contrary, higher hs-CRP (above the median) showed prognostic value for adverse events in MDCM patients (HR 3.19, 95% CI 1.52-6.66, P = 0.002), but not in DCM patients (HR 1.04, 95% CI 0.61-1.79, P = 0.88). Conclusions In patients with MDCM, although no evidence suggested the prognostic role of NT-proBNP, higher level of hs-CRP was associated with outcome, supporting the use of hs-CRP in risk stratification for patients with MDCM.
Severe acute respiratory syndrome (SARS) is a highly infectious disease caused by a novel coronavirus (SARS-CoV). Specific monoclonal antibodies (mAbs) against the SARS-CoV are vital for early diagnosis and pathological studies of SARS. Direct intrasplenic inoculation of plasmid DNA encoding antigen is an effective and fast approach to generate specific mAb when the protein antigen is difficult to prepare or dangerous in use. In this study, we selected one fragment of SARS-CoV spike protein (S1-(3)) as antigenic determinant by immunoinformatics. Single intrasplenic immunization of plasmid DNA encoding S1-(3) induced anti-spike protein antibodies. We established one hybridoma cell line secreting specific mAb and evaluated this mAb with murine leukemia virus pseudotyped with SARS-CoV spike protein (MLV/SARS-CoV). The mAb could recognize the spike protein on the MLV/SARS-CoV-infected Vero E6 cells albeit with no neutralizing effect on the infectivity of the pseudotype virus. Our results show that a single-shot intrasplenic DNA immunization is efficient for the production of specific mAb against SARS spike protein, and a linear epitope of the spike protein is recognized in this study.
Background Various randomized trials have demonstrated that postmastectomy radiotherapy (RT) to the chest wall and comprehensive regional nodal areas improves survival in patients with axillary node-positive breast cancer. Controversy exists as to whether the internal mammary node (IMN) region is an essential component of regional nodal irradiation. Available data on the survival benefit of IMN irradiation (IMNI) are conflicting. The patient populations enrolled in previous studies were heterogeneous and most studies were conducted before modern systemic treatment and three-dimensional (3D) radiotherapy (RT) techniques were introduced. This study aims to assess the efficacy and safety of IMNI in the context of modern systemic treatment and computed tomography (CT)-based RT planning techniques. Methods POTENTIAL is a prospective, multicenter, open-label, parallel, phase III, randomized controlled trial investigating whether IMNI improves disease-free survival (DFS) in high-risk breast cancer with positive axillary nodes (pN+) after mastectomy. A total of 1800 patients will be randomly assigned in a 1:1 ratio to receive IMNI or not. All patients are required to receive ≥ six cycles of anthracycline and/or taxane-based chemotherapy. Randomization will be stratified by institution, tumor location (medial/central vs. other quadrants), the number of positive axillary nodes (1–3 vs. 4–9 vs. ≥10), and neoadjuvant chemotherapy (yes vs. no). Treatment will be delivered with CT-based 3D RT techniques, including 3D conformal RT, intensity-modulated RT, or volumetric modulated arc therapy. The prescribed dose is 50 Gy in 25 fractions or 43.5 Gy in 15 fractions. Tiered RT quality assurance is required. After RT, patients will be followed up at regular intervals. Oncological and toxilogical outcomes, especially cardiac toxicities, will be assessed. Discussion This trial design is intended to overcome the limitations of previous prospective studies by recruiting patients with pN+ breast cancer, using DFS as the primary endpoint, and prospectively assessing cardiac toxicities and requiring RT quality assurance. The results of this study will provide high-level evidence for elective IMNI in patients with breast cancer after mastectomy. Trial registration ClinicalTrails.gov, NCT04320979. Registered 25 Match 2020, https://clinicaltrials.gov/ct2/show/NCT04320979
BackgroundHeart failure (HF) patients are in a hypercoagulable state that predisposes them to an intracardiac thrombus. We aim to assess the clinical features of patients with HF and intracardiac thrombus.MethodsPatients diagnosed with HF with intracardiac thrombus were enrolled in this study. Patients' demographics, clinical comorbidities, laboratory tests, and cardiac imaging parameters are recorded. Baseline characteristics are described; the relationship between intracardiac thrombus location and cardiac underlying diseases, New York Heart Association (NYHA) class, and left ventricular ejection fraction (LVEF) are analyzed; and the anticoagulation rate is summarized.ResultsA total of 1,248 patients were included in the study. Most patients were men (72.2%) with a mean age of 54 years. The left ventricle is the most frequently involved (66.8%), and the prevalence of left ventricular thrombus is more in patients complicated with coronary artery diseases, ventricular noncompaction cardiomyopathy, and dilated cardiomyopathy (86.3%, 86.4%, and 78.2%, respectively). When combined with atrial fibrillation, atrial flutter, hypertrophic cardiomyopathy, restrictive cardiomyopathy, or valvular cardiomyopathy, the intracardiac thrombus is mostly likely to occur in the left atrium. The incidence rate of left cardiac thrombosis increased with the decline of LVEF, an increase of NYHA class, and enlargement of a cardiac chamber. Overall, the anticoagulation rate was 56.8%, with warfarin still the mainstay drug (45.1%), while the prescription of non-vitamin K antagonist oral anticoagulants rose year by year. As for imaging modalities for thrombus detection and diagnosis, transthoracic echocardiography was the most widely performed (75.1%).ConclusionThis study summarizes the underlying disease constitution, thrombus location and related factors, imaging modalities, and antithrombotic profile in HF patients with intracardiac thrombus comprehensively.
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