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Objective: To assess the efficacy and safety of the initiation of sacubitril-valsartan (ARNI) therapy, as compared with ACEI therapy, after hemodynamic stabilization among patients hospitalized for acute decompensated heart failure (ADHF). Methods: A total of 199 hospitalized patients for ADHF in our department from January 2017 to June 2019 were included in this retrospective analysis. According to the medication early after hemodynamic stabilization, patients were divided into ARNI group (n=92) and ACEI group (n=107). Among the included patients, 61 patients with newly diagnosed heart failure at the time of admission were also divided into ARNI group (n=30) and ACEI group (n=31) according to the applied medication. Clinical baseline data and follow-up results of enrolled patients were collected through the electronic medical records at admission, outpatient and telephone follow-up. The primary effectiveness observation index was left ventricular ejection fraction (LVEF) and left ventricular end diastolic dimension (LVEDD) measured by echocardiography; the secondary observation index was death from any causes and hospitalization for heart failure. Safety outcomes were the incidences of symptomatic hypotension, worsening renal function, hyperkalemia, and angioedema. Results: The clinical baseline characteristics were similar between ARNI group and ACEI group(all P>0.05). The duration of follow up was (15.2±6.5) months in all patients enrolled, (12.3±5.0) months in ARNI group, and (18.2±6.5) months in ACEI group. At the end of follow-up, prevalence of an absolute LVEF increase of more than 5% was 48.9% (45/92) in ANRI group and 25.2% (27/107) in ACEI group (P=0.001). Percent of LVEF increase to more than 50% was 17.4% (16/92) in ANRI group and 3.7% (4/107) in ACEI group (P=0.001). Percent of patients with more than 10 mm LVEDD reduction was 14.1% (13/92) in ANRI group and 3.7% (4/107) in ACEI group (P=0.009). All-cause mortality rate was 5.7% (5/88) in ARNI group and 15.3% (13/85) in ACEI group (P=0.038). Rate of re-hospitalization due to heart failure was 50% (46/92) in ARNI group and 71% (76/107) in ACEI group(P=0.002).The rates of symptomatic hypotension, worsening renal function, hyperkalemia, and angioedema were similar between ARNI group and ACEI group (all P>0.05). In patients with first diagnosed heart failure,percent of LVEF increase to more than 50% was 30% (9/30) in ANRI group and 6.5% (2/31) in ACEI group (P=0.017). Percent of more than 10 mm LVEDD reduction was 26.7%(8/30) in ANRI group and 3.2%(1/31) in ACEI group (P=0.012). Percent of an absolute LVEF increase of more than 5% was 53.3% (16/30) in ANRI group and 51.6% (16/31) in ACEI group (P=0.893). Re-hospitalization due to heart failure was 23.3% (7/30) in ARNI group and 73.3% (11/31) in ACEI group(P<0.01). Rate of all-cause death tended to be lower in patients receiving ARNI (3.4% (1/29)) as compared to patients receiving ACEI (13.0% (3/23), P=0.197). Conclusions: Among patients with heart failure with reduced ejection fraction hospitalized for ADHF, the initiation of ARNI therapy after hemodynamic stabilization is associated with a more significant improvement of cardiac remodeling and pump function than ACEI therapy and satisfactory safety. In ADHF patients with first diagnosed heart failure, initiation of ARNI therapy after hemodynamic stabilization can more effectively improve cardiac remodeling and pump function than treatment with ACEI.
Subject(s)
Humans , Aminobutyrates , Angiotensin Receptor Antagonists/therapeutic use , Biphenyl Compounds , Drug Combinations , Heart Failure/drug therapy , Retrospective Studies , Stroke Volume , Tetrazoles , Treatment Outcome , Valsartan , Ventricular Function, LeftABSTRACT
Angiopoietin2( ANGPT2 ) plays an important role in tumor angiopoiesis. ANGPT2 antagonises ANGPT1 resulting in an effect on the stability of blood vessels, which promotes tumor growth, invasion, proliferation as well as relating to tumor vascular density. A lot of researches published papers about anti-ANGPT2 for the treatment of tumor, and have made some progresses. In this review, the role of ANGPT2 in the pathogenesis of acute myelogenous leukemia (AML), including its effects on proliferation of leukemia cells, bone marrow angiopoiesis, tumor invasion and metastasis are briefly summarised in order to provide the basis for targeted ANGPT2 in treatment of AML.
Subject(s)
Humans , Angiopoietin-1 , Allergy and Immunology , Antibodies , Allergy and Immunology , Bone Marrow , Leukemia, Myeloid, Acute , Allergy and Immunology , Neoplasm Invasiveness , Neoplasm MetastasisABSTRACT
<p><b>BACKGROUND</b>Cigarette smoke-induced emphysema is associated with overexpression of the chemokine receptor CXCR3 and its ligands. Previously, we have demonstrated that pentoxifylline (PTX) alleviated cigarette smoke-induced emphysema. The aim of this study was to determine if the overexpression of CXCR3 and its ligand interferon-inducible protein-10 (IP-10) that was elicited by smoke exposure were attenuated by PTX.</p><p><b>METHODS</b>(1) The study in vitro: a given number of RAW264.7 macrophages with decreasing concentrations of PTX in the culture medium were challenged with cigarette smoke extract (CSE); (2) The study in vivo: male BALB/c mice were randomized into four groups, i.e., sham-smoke, smoke only, smoke with 2 mg/kg PTX, and smoke with 10 mg/kg PTX. The smoke exposure time was 90 minutes once a day, 6 days a week for 16 weeks. PTX was given intraperitoneally before each episode of smoke exposure. Interferon (IFN)-γ and IP-10 in broncho-alveolar lavage fluid (BALF) and in culture medium were measured by enzyme-linked immunosorbent assay (ELISA). IP-10 mRNA in lung tissue was assessed by RT-PCR. CXCR3 positive cells in lung sections were visualized by immunochemistry staining.</p><p><b>RESULTS</b>Up-regulation of IFN-γ and IP-10 in the culture medium of macrophages elicited by CSE was inhibited by PTX in a dose-dependent manner. Chronic cigarette smoke exposure led to overexpression of IFN-γ and IP-10 in BALF, upregulation of IP-10 mRNA and increased infiltration of CXCR3(+) cells into lung parenchyma. Administration of PTX decreased the level of IFN-γ from (6.26 ± 1.38) ng/ml to (4.43 ± 0.66) ng/ml by low dose PTX or to (1.74 ± 0.28) ng/ml by high dose PTX. IP-10 was reduced from (10.35 ± 1.49) ng/ml to (8.19 ± 0.79) ng/ml by low dose PTX or to (7.51 ± 0.60) ng/ml by high dose PTX. The expression of IP-10 mRNA was also down-regulated (P < 0.05). But only with a high dose of PTX was the ratio of CXCR3(+) cells decreased; 15.2 ± 7.3 vs. 10.4 ± 1.8 (P < 0.05).</p><p><b>CONCLUSION</b>PTX attenuates cigarette smoke-induced overexpression of chemokine receptor CXCR3 and its ligand IP-10, which is relevant to its inhibitory effect on pulmonary emphysema.</p>
Subject(s)
Animals , Male , Mice , Cell Line , Chemokine CXCL10 , Genetics , Metabolism , Gene Expression , Immunohistochemistry , Mice, Inbred BALB C , Pentoxifylline , Pharmacology , Therapeutic Uses , Pulmonary Emphysema , Drug Therapy , Genetics , Metabolism , Random Allocation , Receptors, CXCR3 , Genetics , Metabolism , Reverse Transcriptase Polymerase Chain Reaction , SmokingABSTRACT
Objective To explore the correlation between the findings ofbrainstem reflex (BSR)and the prognosis of consciousness in long-term unconscious patients with severe traumatic brain injury (TBI).Methods BSR findings were collected in 60 patients,admitted to our hospital from March 2010 to June 2011 and suffered from severe TBI with a duration of disturbance of consciousness≥2weeks.The patients were divided into conscious and unconscious groups based on whether or not the patients were still with disturbance of consciousness 6 months after the injury.And finally,the significant indicators were chosen in the two groups using chi square test.Results A total of 36 patients (60.0%)retrieved consciousness 6 months after the injury.The abnormality rate of BSR was 23.8%.Significant differences were noted between conscious and unconscious groups in the disappearance of left ciliospinal reflex,left vertical oculo-vestibular reflex,double light reflex and oculocardiac reflex.The unconscious probabilities in patients with abnormal BSR which indexes mentioned above were higher.Conclusion The findings of BSR can objectively and accurately demonstrate the degree of cerebral dysfunction and predict the prognosis of consciousness.
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Objective To explore the correlation between brainstem auditory evoked potential (BAEP) findings and outcome in long-term unconscious patients with severe traumatic brain injury (TBI).Methods BAEP findings were recorded and analyzed in 63 patients suffering from severe TBI with duration of disturbance of unconsciousness for more than 2 weeks. The peak latency (PL) of wave Ⅰ, Ⅲ and Ⅴ, the interpeak latency (IPL) of wave Ⅰ-Ⅲ and Ⅲ-Ⅴ and the amplitude ratio of wave Ⅰ and Ⅴ were analyzed. Conscious or unconscious at 6 months after the injury was considered as the outcome criterion,and based on these, the patients were divided into conscious and unconscious groups; the significant indicators were chosen in the 2 groups using independent-sample t test. Results The probabilities of awakening in these patients were 34.9% (22/63) with abnormal index of BAEP indicators reaching 66.7%. Sixteen patients were sober at last in 21 patients with normal PL of wave Ⅰ, Ⅲ and Ⅴ, IPL of wave Ⅰ-Ⅲ and Ⅲ-Ⅴ, and amplitude ratio of wave Ⅰ and Ⅴ in bilateral side (the probabilities of awakening were 76.2%); 8 patients having abnormal PL of wave Ⅴ in bilateral side and 7 having abnormal IPL of wave Ⅲ-Ⅴ in bilateral side were unconscious; 2 patients having disappeared wave Ⅴ in unilateral side were unconscious. PL of wave Ⅴ and IPL of wave Ⅲ-Ⅴ in bilateral side were significantly different between the conscious group and the unconscious group. (P<0.05). Conclusion BAEP findings (PL of wave Ⅴ and IPL of wave Ⅲ-Ⅴ in bilateral side) can objectively and accurately demonstrate the cerebral dysfunction and predict the outcome of the patients.
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Objective To study the relationship between O6-methylguanine-DNA-methyltransferase(MGMT)expression in gliomas and the efficacy of teniposide(VM-26)combined with somustine(Me-CCNU). Methods A retrospective chart review was performed on 47 patients diagnosed by pathology as having gliomas.The expression of MGMT in all paraffin sections of the patients were determined by immunohistochemical technique.The clinical efficacy was observed and the overall survival rates were analyzed. Results The positive rate of MGMT in all the 47 patients was 40.4%.Three-year survival rate of the negative group was 66.7%and that of the positive group was 52.6%without statistical significance(P>0.05).The average OS of the negative group was 67.861±10.094 and that of the positive group was 47.263±7.983 without statistical significance(P>0.05).Bone marrow suppression of grade I was found in 11 patients with 6 appearing stomach discomfort,vomiting,diarrhea,loss of appetite and digestive symptoms.Conclusions MGMT is one agent of drug resistance of nitrosourea.VM-26 combined with Me-CCNU chemotherapy can overcome the resistance effect of MGMT with little side effects.
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Objective To investigate the relationship between MRI classification and both time of awakening and prognosis in patients with long-term consciousness disorders after traumatic brain injury. Methods Sixty-six patients, admitted to our hospital from 2003 to 2008 and suffered from severe traumatic brain injury with consciousness disorders for more than 2 weeks, were collected. The cranial MRI data of all patients were recorded and classified; the awakening time of all conscious patients after injury was recorded; the prognoses were judged by Glasgow outcome scale 6 month after the injury.The relationship between MRI classification and both time of awakening and prognosis were analyzed.Results The prognoses (the scores of Glasgow outcome scale) were closely associated with the cranial MRI classification; the higher the MRI classification, the poorer the prognosis; the accuracy rate of MRI in assessing the prognosis was 83.33%. The average awakening times were (8.00±4.10) weeks in patients with graded Ⅰ and Ⅱa of MRI classification, and (22.67±23.66) weeks in patients with graded Ⅱb and Ⅲ of MRI classification. Conclusions The MRI classification is correlative to the prognosis and the awakening time of the patients with long-term consciousness disorders after severe traumatic brain injury.Using MRI classification can objectively and accurately evaluate patients' prognosis.