Cardiovascular Drugs and Therapy - Available animal models of acute heart failure (AHF) and their limitations are discussed herein. A novel and preclinically relevant porcine model of decompensated... 相似文献
In December 2019 a novel coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), started spreading from Wuhan city of Chinese Hubei province and rapidly became a global pandemic. Clinical symptoms of the disease range from paucisymptomatic disease to a much more severe disease. Typical symptoms of the initial phase include fever and cough, with possible progression to acute respiratory distress syndrome. Gastrointestinal manifestations such as diarrhoea, vomiting and abdominal pain are reported in a considerable number of affected individuals and may be due to the SARS-CoV-2 tropism for the peptidase angiotensin receptor 2. The intestinal homeostasis and microenvironment appear to play a major role in the pathogenesis of COVID-19 and in the enhancement of the systemic inflammatory responses. Long-term consequences of COVID-19 include respiratory disturbances and other disabling manifestations, such as fatigue and psychological impairment. To date, there is a paucity of data on the gastrointestinal sequelae of SARS-CoV-2 infection. Since COVID-19 can directly or indirectly affect the gut physiology in different ways, it is plausible that functional bowel diseases may occur after the recovery because of potential pathophysiological alterations (dysbiosis, disruption of the intestinal barrier, mucosal microinflammation, post-infectious states, immune dysregulation and psychological stress). In this review we speculate that COVID-19 can trigger irritable bowel syndrome and we discuss the potential mechanisms. 相似文献
The recognition that neurogenesis does not stop with adolescence has spun off research towards the reduction of brain disorders by enhancing brain regeneration. Adult neurogenesis is one of the tougher problems of developmental biology as it requires the generation of complex intracellular and pericellular anatomies, amidst the danger of neuroinflammation. We here review how a multitude of regulatory pathways optimized for early neurogenesis has to be revamped into a new choreography of time dependencies. Distinct pathways need to be regulated, ranging from neural growth factor induced differentiation to mitochondrial bioenergetics, reactive oxygen metabolism, and apoptosis. Requiring much Gibbs energy consumption, brain depends on aerobic energy metabolism, hence on mitochondrial activity. Mitochondrial fission and fusion, movement and perhaps even mitoptosis, thereby come into play. All these network processes are interlinked and involve a plethora of molecules. We recommend a deep thinking approach to adult neurobiology. 相似文献
BackgroundThe efficacy of ticagrelor in the long-term post–ST-segment elevation myocardial infarction (STEMI) treated with fibrinolytic therapy remains uncertain.ObjectivesThe purpose of this study was to evaluate the efficacy of ticagrelor when compared with clopidogrel in STEMI patients treated with fibrinolytic therapy.MethodsThis international, multicenter, randomized, open-label with blinded endpoint adjudication trial enrolled 3,799 patients (age <75 years) with STEMI receiving fibrinolytic therapy. Patients were randomized to ticagrelor (180-mg loading dose, 90 mg twice daily thereafter) or clopidogrel (300- to 600-mg loading dose, 75 mg daily thereafter). The key outcomes were cardiovascular mortality, myocardial infarction, or stroke, and the same composite outcome with the addition of severe recurrent ischemia, transient ischemic attack, or other arterial thrombotic events at 12 months.ResultsThe combined outcome of cardiovascular mortality, myocardial infarction, or stroke occurred in 129 of 1,913 patients (6.7%) receiving ticagrelor and in 137 of 1,886 patients (7.3%) receiving clopidogrel (hazard ratio: 0.93; 95% confidence interval: 0.73 to 1.18; p = 0.53). The composite of cardiovascular mortality, myocardial infarction, stroke, severe recurrent ischemia, transient ischemic attack, or other arterial thrombotic events occurred in 153 of 1,913 patients (8.0%) treated with ticagrelor and in 171 of 1,886 patients (9.1%) receiving clopidogrel (hazard ratio: 0.88; 95% confidence interval: 0.71 to 1.09; p = 0.25). The rates of major, fatal, and intracranial bleeding were similar between the ticagrelor and clopidogrel groups.ConclusionAmong patients age <75 years with STEMI, administration of ticagrelor after fibrinolytic therapy did not significantly reduce the frequency of cardiovascular events when compared with clopidogrel. (Ticagrelor in Patients With ST Elevation Myocardial Infarction Treated With Pharmacological Thrombolysis [TREAT]; NCT02298088) 相似文献
Introduction: Allergic rhinitis (AR) is the most common allergic disease, and it has a relevant impact on the quality of life of the patient. Treatment of AR includes a combination of strategies of proven efficacy and effectiveness; however, a relevant proportion of patients remain uncontrolled.
Areas covered: This review article summarizes emerging therapeutic approaches to AR; these approaches include nasal sprays, oral drugs, alternative allergen immunotherapy administration routes, and biologic agents.
Expert opinion: The agents discussed require further clinical trials to prove their efficacy in the treatment of AR. Some of these agents, in particular, allergen immunotherapies and biologics, have the potential to form crucial precision medicine approaches to AR. Those that prove their efficacy in clinical trials must also be evaluated from a pharmacoeconomic perspective, possibly in real-life studies; this will define which therapeutic strategies achieve the most convenient and cost-effective ratio, thus yielding a novel opportunity for the most severe and previously treatment-resistant allergic patients. 相似文献
In colorectal cancer liver metastases (CRCLM), bevacizumab-based neoadjuvant strategies provide increased pathologic response. We aimed at assessing the activity of perioperative capecitabine, oxaliplatin, irinotecan, and bevacizumab (COI-B regimen) in patients with potentially resectable CRCLM, and investigating biomarkers for early prediction of pathologic response.
Patients and Methods
This was a single-center phase II study enrolling patients with liver-limited, borderline resectable disease and/or high-risk features. Patients received 5 preoperative and 4 postoperative cycles of biweekly COI-B (irinotecan 180 mg/m2 and bevacizumab 5 mg/Kg on day 1, oxaliplatin 85 mg/m2 on day 2, and capecitabine 1000 mg/m2 twice a day on days 2 to 6). The primary endpoint was pathologic response rate in the intention-to-treat population. A Simon 2-stage design was adopted to detect an increase from 30% to 50% with a power of 90%. Dynamic imaging biomarkers (early tumor shrinkage [ETS], deepness of response, maximum standardized uptake volume [SUVmax]/regression index) and next generation sequencing data were explored as surrogates.
Results
From June 2013 to March 2017, 46 patients were enrolled. Pathologic response was achieved in 63% patients (endpoint met), and responders achieved significantly better survival outcomes with respect to non-responders. The most frequent grade 3/4 adverse events were diarrhea and neutropenia (8.7%) in the preoperative phase and thromboembolic events (5.9%) in the postoperative phase. ETS and lower SUV-2 were significantly associated with pathologic response.
Conclusion
The COI-B regimen is a feasible and highly active perioperative strategy in patients with molecularly unselected, potentially resectable CRCLM. ETS and SUV-2 have a promising role as imaging-based biomarkers for pathologic response. 相似文献