Résumé
BACKGROUND@#Acute heart failure (AHF) is the most common disease in emergency departments (EDs). However, clinical data exploring the outcomes of patients presenting AHF in EDs are limited, especially the long-term outcomes. The purposes of this study were to describe the long-term outcomes of patients with AHF in the EDs and further analyze their prognostic factors.@*METHODS@#This prospective, multicenter, cohort study consecutively enrolled 3335 patients with AHF who were admitted to EDs of 14 hospitals from Beijing between January 1, 2011 and September 23, 2012. Kaplan-Meier and Cox regression analysis were adopted to evaluate 5-year outcomes and associated predictors.@*RESULTS@#The 5-year mortality and cardiovascular death rates were 55.4% and 49.6%, respectively. The median overall survival was 34 months. Independent predictors of 5-year mortality were patient age (hazard ratio [HR]: 1.027, 95 confidence interval [CI]: 1.023-1.030), body mass index (BMI) (HR: 0.971, 95% CI: 0.958-0.983), fatigue (HR: 1.127, 95% CI: 1.009-1.258), ascites (HR: 1.190, 95% CI: 1.057-1.340), hepatic jugular reflux (HR: 1.339, 95% CI: 1.140-1.572), New York Heart Association (NYHA) class III to IV (HR: 1.511, 95% CI: 1.291-1.769), heart rate (HR: 1.003, 95% CI: 1.001-1.005), diastolic blood pressure (DBP) (HR: 0.996, 95% CI: 0.993-0.999), blood urea nitrogen (BUN) (HR: 1.014, 95% CI: 1.008-1.020), B-type natriuretic peptide (BNP)/N-terminal pro-B-type natriuretic peptide (NT-proBNP) level in the third (HR: 1.426, 95% CI: 1.220-1.668) or fourth quartile (HR: 1.437, 95% CI: 1.223-1.690), serum sodium (HR: 0.980, 95% CI: 0.972-0.988), serum albumin (HR: 0.981, 95% CI: 0.971-0.992), ischemic heart diseases (HR: 1.195, 95% CI: 1.073-1.331), primary cardiomyopathy (HR: 1.382, 95% CI: 1.183-1.614), diabetes (HR: 1.118, 95% CI: 1.010-1.237), stroke (HR: 1.252, 95% CI: 1.121-1.397), and the use of diuretics (HR: 0.714, 95% CI: 0.626-0.814), β-blockers (HR: 0.673, 95% CI: 0.588-0.769), angiotensin-converting enzyme inhibitors (ACEIs) (HR: 0.714, 95% CI: 0.604-0.845), angiotensin-II receptor blockers (ARBs) (HR: 0.790, 95% CI: 0.646-0.965), spironolactone (HR: 0.814, 95% CI: 0.663-0.999), calcium antagonists (HR: 0.624, 95% CI: 0.531-0.733), nitrates (HR: 0.715, 95% CI: 0.631-0.811), and digoxin (HR: 0.579, 95% CI: 0.465-0.721).@*CONCLUSIONS@#The results of our study demonstrate poor 5-year outcomes of patients presenting to EDs with AHF. Age, BMI, fatigue, ascites, hepatic jugular reflux, NYHA class III to IV, heart rate, DBP, BUN, BNP/NT-proBNP level in the third or fourth quartile, serum sodium, serum albumin, ischemic heart diseases, primary cardiomyopathy, diabetes, stroke, and the use of diuretics, β-blockers, ACEIs, ARBs, spironolactone, calcium antagonists, nitrates, and digoxin were independently associated with 5-year all-cause mortality.
Sujets)
Humains , Antagonistes des récepteurs aux angiotensines , Inhibiteurs de l'enzyme de conversion de l'angiotensine , Pékin/épidémiologie , Marqueurs biologiques , Études de cohortes , Service hospitalier d'urgences , Études de suivi , Défaillance cardiaque/mortalité , Peptide natriurétique cérébral , Fragments peptidiques , Pronostic , Études prospectivesRésumé
Objective: To analyze the clinical and genetic characteristics of clinical subtypes of non-obstructive hypertrophic cardiomyopathy (HCM). Methods: It was a cohort study. Patients with non-obstructive HCM admitted to Fuwai Hospital, Chinese Academy of Medical Sciences, from January 1999 to April 2019 were enrolled. According to the characteristics of cardiac morphology and function shown by echocardiography, the patients were divided into common type, dilated type, restricted type and reduced ejection fraction type. The clinical data of the patients were recorded, and 8 sarcomere pathogenic genes were screened by full exon sequencing or panel sequencing. Patienst were followed up and cardiovascular endpoint events were recorded. Results: A total of 815 patients with non-obstructive HCM were enrolled, including 27 (3.3%) restricted type, 51 (6.3%) dilated type, 30 (3.7%) reduced ejection fraction type and 707 (86.7%) common type. A total of 704 out of 815 patients underwent genetic testing. Among them, 299 (42.5%) patients carried at least 1 sarcomere gene mutation. MYBPC3 and MYH7 mutation accounted for 42.1% (126/299) and 35.8% (107/299) respectively. 66.7% (16/24) of the patients with restricted type carried sarcomere gene mutation, which was higher than that in patients with dilated type (36.4% (16/44)) and in common type (41.5% (250/602), P=0.015). Among the patients with reduced ejection fraction, 56.7% (17/30) patients carried sarcomere gene mutations, 23.3% (7/30) carried multiple sarcomere mutations, which was higher than that in restricted type (8.3% (2/24)), in dilated type (9.1% (4/44)) and in common type 4.2% ((24/577), P<0.001). MYH7 and MYBPC3 were the main mutation gene types of all clinical subtypes, and the genotypes were similar among groups (all P>0.05). Seven hundred and three out 815 patients were followed up for 2.9 (1.4, 4.0) years. There were 53(7.5%) cardiovascular death. Cardiovascular death occurred in 5.0% (29/578) patients with common type, 13.0% (3/23) patients with restricted type, 16.3% (7/43) patients with dilated type and 46.7% (14/30) patients with decreased ejection fraction. Univariate Cox proportional hazards model analysis showed that the risk of cardiovascular death in patients with restricted, dilated and reduced ejection fraction type was higher than that in patients with common type (P<0.001). After adjusting for gender, age of onset, body mass index, history of hypertension, coronary heart disease and diabetes, multivariate Cox proportional hazards model analysis showed that the HR of cardiovascular death in patients with restricted, dilated and reduced ejection fraction type were 5.454 (95%CI 1.137-26.157, P=0.034) and 6.597 (95%CI 1.632-26.667, P=0.008) and 9.028 (95%CI 2.201-37.039, P=0.002) respectively, as compared to patients with common type. Conclusions: Most of the patients with non-obstructive HCM are common type, featured by mild clinical manifestations and good prognosis. Although the proportion of restricted type and dilated type is relatively low, and cardiac systolic function is mostly preserved, the clinical phenotype and prognosis of these patients are similarly severe and poor as patients with reduced ejection fraction. The genotypes are similar in different clinical subtypes, but the proportion of patients with sarcomere gene mutation is higher in restricted type, and the proportion of patients with multiple sarcomere gene mutation is higher in decreased ejection fraction type.
Sujets)
Humains , Cardiomyopathie hypertrophique/génétique , Études de cohortes , Mutation , Phénotype , Sarcomères/génétiqueRésumé
OBJECTIVE@#To investigate the effect of Rictor on the hematopoiesis of fetal liver by specific knock-out of Rictor in hematopoietic cells of Vav-Cre mice.@*METHODS@#E12.5 0.08ee fetal liver cells from the experimental group Vav-Cre; Rictor embryos and control group Rictor or Rictor embryos were transplanted to recipients respectively to observe the effect of Rictor on reconstitution ability of hematopoietic stem cells. In the meantime, E14.5 0, 10, 20, 40, 60, 80 sorted hematopoietic stem cells from the Vav-Cre; Rictor fetal liver of experimental group and Rictor or Rictor fetal liver of control group were transplanted in to recipients to analyze the numbers of functional hematopoietic stem cells after Rictor was knocked-out. Furthermore, the self-renewal capacity was investigated by secondary transplantation of BM cells from primary recipients that had been successfully repopulated with E12.5 fetal liver-derived cells and by cell cycle analysis.@*RESULTS@#All the recipients receiving E12.5 Rictor or Rictor cells were repopulated (8/8, from 2 independent experiments) with an average chimerism of 77.2%±11.1% at 4 months post-transplantation, which resulted in 57 LT-RU per FL. In comparison, 8 out of 8 recipients receiving Vav-Cre; Rictor cells were repopulated with significantly reduced chimerism (37.0%±16.3%) (P<0.01), which was equivalent to 8 LT-RU per FL. The limiting dilution transplantation experiment showed that there was one functional hematopoietic stem cell out of 17 sorted SLAM cells in the control group, and one functional hematopoietic stem cell out of 39 sorted SLAM cells in the experimental group. The secondary transplantation experiments showed that 2 out of 4 recipients were reconstructed in the control group after 1 month, and 0 was reconstructed in the experimental group by transplanting 4×10 donor cells respectively. What's more, the percentage of S/G/M cells in the experimental group increased when compared with controls.@*CONCLUSION@#In the process of fetal liver hematopoiesis, the specifically knocking-out the Rictor in hematopoietic system can lead to defect of reconstitution ability, decrease of the functional hematopoietic stem cell numbers and reduction of self-renewal ability of hematopoietic stem cells.
Sujets)
Animaux , Souris , Foetus , Hématopoïèse , Transplantation de cellules souches hématopoïétiques , Cellules souches hématopoïétiques , Foie , Compagnon de mTOR insensible à la rapamycineRésumé
Objective: To explore the role of PDK1 in the transition of endothelial to hematopoietic cells and its effect on the generation and normal function of HSC. Methods: PDK1 was deleted specifically in endothelial cells expressing VEC (Vascular Endothelial Cadherin). CFU-C was performed to detect the effect of PDK1 on the function of hematopoietic progenitor cells using the cells from PDK1(fl/fl), PDK1(fl/+) and Vec-Cre; PDK1(fl/fl) AGM region. Hematopoietic stem cell transplantation assay was conducted to determine the effect of PDK1 on hematopoietic stem cells. Flow cytometry was performed to analyze the influence of PDK1 on percentage, cell cycle and apoptosis of CD31(+)c-Kit(high) cell population. Real-time PCR was conducted to measure the expression of transcription factors involved in process of transition from endothelial to hematopoietic cells. Results: In contrast to the wild type group, the CFU from PDK1-deficient hematopoietic progenitor cells showed smaller in morphology and fewer in quantity. CFU-GM was (24±5)/ee in knockout group, and the control group was (62±1)/ee (P=0.001). PDK1 deletion severely impaired the ability to repopulate hematopoietic cells and differentiate into committed cells. hematopoietic progenitor cells from knockout group was transplanted into 5 recipients without any recipients reconstructed. However, 5 of 7 recipients were reconstructed in control group (P=0.001). The proportion of intra-vascular clusters in the AGM was decreased (the frequency of CD31(+)c-Kit(high) in the knockout group was (0.145±0.017)%, and the control group ratio was (0.385±0.040)% (P=0.001), but not due to the inhibition of cell proliferation and/or increase of apoptosis. Further study found that the absence of endothelial PDK1 causes a decreased expression of RUNX1, P2-RUNX1, GATA2 and other important hematopoietic-related transcription factors in hemogenic cluster. Conclusion: PDK1 deletion impairs the transition of endothelial cells to hematopoietic cells as well as the generation and function of HSC.
Sujets)
3-Phosphoinositide-dependent protein kinases , Aorte , Cellules endothéliales , Gonades , Hématopoïèse , Transplantation de cellules souches hématopoïétiques , Cellules souches hématopoïétiques , Mésonéphros , Protéines proto-oncogènes c-kitRésumé
Objectives:To observe the clinical and coronary artery computed tomography(CT) characteristics of patients with ankylosing spondylitis. Methods:Data from 33 consecutive patients with ankylosing spondylitis admitted due to chest discomfort in Fuwai Hospital from January 2014 to June 2017 were analyzed, 33 age and sex matched patients with no ankylosing spondylitis were selected as the control group. Coronary artery CT features was compared between the two groups. Results:Incidence of hypertension, smoking, diabetes and hyperlipidemia, BMI values were similar between the two groups. Blood lipid level (high density lipoprotein cholesterol, low density lipoprotein cholesterol, triglyceride and, total cholesterol), creatinine and uric acid values were also similar between the two groups. Erythrocyte sedimentation rate (ESR) ([14.15±12.81]m/s vs [7.79±6.26]m/s, P=0.013) and high C-reactive protein (hs-CRP) ([6.88±5.65]ng/L vs [3.16±3.13]ng/L, P=0.002) values were significantly higher in ankylosing spondylitis group than in the control group. Percent of coronary artery stenosis (>50%) was significantly higher in ankylosing spondylitis group than in the control group (23[69.7%] vs 14[42.4%], P=0.026). Coronary artery calcification was significantly higher in ankylosing spondylitis group than in the control group (22 [66.7%] vs 9[27.3%], P=0.001). Conclusions:Degree of coronary artery stenosis and calcification as well as inflammatory index (ESR and hs-CRP) are significantly higher in ankylosing spondylitis patients compared to control patients.
Résumé
<p><b>BACKGROUND</b>The emergency department (ED) has a pivotal influence on the management of acute heart failure (AHF), but data concerning current ED management are scarce. This Beijing AHF Registry Study investigated the characteristics, ED management, and short- and long-term clinical outcomes of AHF.</p><p><b>METHODS</b>This prospective, multicenter, observational study consecutively enrolled 3335 AHF patients who visited 14 EDs in Beijing from January 1, 2011, to September 23, 2012. Baseline data on characteristics and management were collected in the EDs. Follow-up data on death and readmissions were collected until November 31, 2013, with a response rate of 92.80%. The data were reported as median (interquartile range) for the continuous variables, or as number (percentage) for the categorical variables.</p><p><b>RESULTS</b>The median age of the enrolled patients was 71 (58-79) years, and 46.84% were women. In patients with AHF, coronary heart disease (43.27%) was the most common etiology, and myocardium ischemia (30.22%) was the main precipitant. Most of the patients in the ED received intravenous treatments, including diuretics (79.28%) and vasodilators (74.90%). Fewer patients in the ED received neurohormonal antagonists, and 25.94%, 31.12%, and 33.73% of patients received angiotensin converting enzyme inhibitors/angiotensin receptor blockers, beta-blockers, and spironolactone, respectively. The proportions of patients who were admitted, discharged, left against medical advice, and died were 55.53%, 33.58%, 7.08%, and 3.81%, respectively. All-cause mortalities at 30 days and 1 year were 15.30% and 32.27%, respectively.</p><p><b>CONCLUSIONS</b>Substantial details on characteristics and ED management of AHF were investigated. The clinical outcomes of AHF patients were dismal. Thus, further investigations of ED-based therapeutic approaches for AHF are needed.</p>
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<p><b>OBJECTIVE</b>To investigate the restoration of rat penile erection by reconstructing injured cavernous nerves (CN) with a compound graft prepared from porcine small intestinal submucosa (SIS) and Schwann cells (SC).</p><p><b>METHODS</b>SCs were cultured in vitro and a compound graft was prepared from the SCs and SIS. Thirty-three healthy SD rats were randomly divided into three groups of equal number, sham-operation, CN ablation, and SIS + SC graft. Three months after the operation, all the rats underwent the apomorphine test, followed by immunohistochemical staining of the tissues from the middle part of the corpus cavernosum penis.</p><p><b>RESULTS</b>Combined use of mechanical stripping, mixed-enzyme digestion, different-speed adhesion, short-term Ara-C and some other methods yielded SCs of a purity high enough for nerve tissue engineering. The SIS prepared by mechanical and chemical methods exhibited a good biocompatibility with SCs, which could adhere, grow, propagate and differentiate on its surface. The apomorphine test showed that both the rate and frequency of penile erection were significantly higher in the SIS + SC graft than in the CN ablation group (P < 0.01), but lower than in the sham operation group (P < 0.01). The number of nNOS positive nerve fibers in the SIS + SC graft group was significantly different from that of the CN ablation (P < 0.01), but both were smaller than that of the sham-operation group.</p><p><b>CONCLUSION</b>The compound of SIS with SCs, as a nerve graft, can be used to reconstruct injured cavernous nerves, and to some extent, restore penile erectile function.</p>