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21.

Background

Epidemiology of patients with worsening heart failure and reduced ejection fraction (HFrEF) in the real-world setting is not well described.

Objectives

The purpose of this study was to describe incidence, clinical characteristics, treatment, and outcomes of patients with HFrEF who develop worsening heart failure (HF) in the real-world setting.

Methods

Data on patients with incident HFrEF from the National Cardiovascular Data Registry PINNACLE were linked to pharmacy, private practitioner, and hospital claims databases. Incidence, clinical characteristics, treatment (angiotensin-converting enzyme inhibitor/angiotensin receptor blocker, beta-blocker, and mineralocorticoid receptor antagonist) and outcomes of patients with worsening HF, defined as ≥90 days of stable HF with subsequent worsening requiring intravenous diuretic agents, were assessed.

Results

Of 11,064 HFrEF patients, 1,851 (17%) developed worsening HF on average 1.5 years following initial HF diagnosis. Patients who developed worsening HF were more likely to be African American, be octogenarians, and have higher comorbidity burden (p < 0.001). At the onset of worsening HF, 42.4% of patients were on monotherapy, 43.4% were on dual therapy, and 14.1% were on triple therapy. A total of 48%, 61%, and 98% of patients were on >50% target dose for angiotensin-converting enzyme inhibitor/angiotensin receptor blocker, beta-blocker, and mineralocorticoid receptor antagonist, respectively. The 2-year mortality rate was 22.5%, and 56% of patients were rehospitalized within 30 days of the worsening HF event.

Conclusions

In the real-world setting, 1 in 6 patients with HFrEF develop worsening HF within 18 months of HF diagnosis. These patients have a high risk for 2-year mortality and recurrent HF hospitalizations. The use of standard-of-care therapies both before and after the onset of worsening HF is low. With high unmet medical need, patients with worsening HF require novel treatment strategies as well as greater optimization of existing guideline-directed therapy.  相似文献   
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Background

Rosacea is a chronic inflammatory skin condition whose etiology has been linked to mast cells and the antimicrobial peptide cathelicidin LL-37. Individuals with refractory disease have demonstrated clinical benefit with periodic injections of onabotulinum toxin, but the mechanism of action is unknown.

Objectives

To investigate the molecular mechanism by which botulinum toxin improves rosacea lesions.

Methods

Primary human and murine mast cells were pretreated with onabotulinum toxin A or B or control. Mast cell degranulation was evaluated by β-hexosaminidase activity. Expression of botulinum toxin receptor Sv2 was measured by qPCR. The presence of SNAP-25 and VAMP2 was established by immunofluorescence. In vivo rosacea model was established by intradermally injecting LL-37 with or without onabotulinum toxin A pretreatment. Mast cell degranulation was assessed in vivo by histologic counts. Rosacea biomarkers were analyzed by qPCR of mouse skin sections.

Results

Onabotulinum toxin A and B inhibited compound 48/80-induced degranulation of both human and murine mast cells. Expression of Sv2 was established in mouse mast cells. Onabotulinum toxin A and B increased cleaved SNAP-25 and decreased VAMP2 staining in mast cells respectively. In mice, injection of onabotulinum toxin A significantly reduced LL-37-induced skin erythema, mast cell degranulation, and mRNA expression of rosacea biomarkers.

Conclusions

These findings suggest that onabotulinum toxin reduces rosacea-associated skin inflammation by directly inhibiting mast cell degranulation. Periodic applications of onabotulinum toxin may be an effective therapy for refractory rosacea and deserves further study.  相似文献   
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Though cerebrovascular complications of pregnancy remain relatively rare, they represent a potentially devastating event that necessitates prompt identification and treatment. Eighteen percent of strokes occurring in young women are linked to pregnancy. They occur mostly in the third trimester or during the post-partum period. Their biggest risk factors are hypertension, preeclampsia/eclampsia and migraine. Cerebrovascular events occurring during this period may involve specific pathophysiological processes that include embolic phenomena or endothelial dysfunction, but can also have common etiologies that are simply favored by the context of pregnancy. Thus, posterior encephalopathy and vasoconstriction cerebral syndrome are relatively frequently involved in cerebrovascular complications of pregnancy. Other very specific causes like amniotic fluid embolism or postpartum cardiomyopathy can also be responsible for such events. The management of stroke during pregnancy must be multidisciplinary and include a neurovascular expertise. Some conditions can lead to a long-life follow-up and modify the management of a future pregnancy.  相似文献   
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Objectives:To assess low dose altepase outcome and safety in comparison with a standard-dose regimen for acute ischemic stroke treatment in Egyptian patients.Materials:An observational prospective cohort non-randomized single blinded study was carried out during the period from November 2017 to December 2018. Eighty Egyptian acute ischemic stroke patients, all eligible for intravenous alteplase, were subdivided into 2 groups (40 patients in each group). Patients were thrombolysed at a dose of 0.6 mg/kg in the first group and 0.9 mg/kg in the second group. Both groups were compared in regard to safety and outcome. Safety was expressed by the rate of symptomatic intracranial hemorrhage (SICH) and 3 months mortality, while outcome was expressed by favorable outcomes at three months (modified Rankin Scale [mRS] of 0 to 2).Results:In the first group, 69.2% (n=27) achieved favorable outcomes at 90 days compared with 64.1% (n=25) in the second group (p=0.631). Ninety-day mortality was 5% (n=2) in the first group versus 2.5% (n=1) in the second group (p=0.556). Symptomatic intracranial hemorrhage was noted in 3 patients in the second group and zero patients in the first group (p=0.077).Conclusion:Low-dose alteplase could be a practical alternative for Egyptian populations with acute ischemic stroke especially in 3 to 4.5 hours window.

Cerebrovascular stroke is the second death and the seventh disability leading cause worldwide.1 Tissue-type plasminogen activator (tPA) alteplase was the first medication approved by the Food and Drug Administration (FDA) for the acute ischemic stroke (AIS) treatment on June 1996, within 3 hours of stroke onset with a recommended dose of 0.9 mg/kg (maximum 90mg).2 In 2008, the safety of using alteplase within 3 to 4.5 hours of stroke onset was approved by the Safe Implementation of Treatments in Stroke International Stroke Thrombolysis Registry (SITS -ISTR)3 and the European Cooperative Acute Stroke Study (ECASS III).4 However, thrombolytic therapy use has not been widely adopted, especially in developing countries. The restricted time window (3 to 4.5 hours), intracerebral hemorrhage (ICH) risk and the drug high cost are major obstacles preventing its broad application.5 Coagulation and fibrinolysis responses differ among different races, which increase symptomatic intracerebral hemorrhage (SICH) risk with standard-dose alteplase6 in Asian populations, many Asian neurologists considered alteplase low dose to be a better alternative for ischemic stroke treatment. Many studies had been conducted in order to prove the efficacy and safety of Alteplase low dose.7-9 One of these studies was the Japan Alteplase Clinical Trial (J-ACT) conducted by Yamaguchi et al10 According to this study, using a 0.6 mg/kg dose of intravenous recombinant tissue plasminogen activator (rtPA) in Japanese patients was safe and effective. Despite the relatively stroke high rate among Egyptian populations, 963/100,000 inhabitants, only less than 1% of stroke patients receive intravenous thrombolysis. A major reason for this is the drug cost.11,12 Low-dose regimens (0.6 mg/kg) use will lower the economic burden of thrombolytic therapy in the community and will greatly promote the implementation of this therapy in Egypt. Our study aim was to assess the outcome and safety of alteplase low dose in comparison to the standard-dose regimen in AIS treatment in Egypt.  相似文献   
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