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OBJECTIVES The study sought to examine the risk of ischemic events and bleeding episodes associated with differing antithrombotic strategies in patients undergoing transcatheter aortic valve replacement (TAVR) with concomitant atrial fibrillation (AF).BACKGROUND Guidelines recommend antiplatelet therapy (APT) post-TAVR to reduce the risk of stroke. However, data on the efficacy and safety of this recommendation in the setting of a concomitant indication for oral anticoagulation (due to atrial fibrillation [AF]) with a vitamin K antagonist (VKA) are scarce.METHODS A multicenter evaluation comprising 621 patients with AF undergoing TAVR was undertaken. Post-TAVR prescriptions were used to determine the antithrombotic regimen used according to the following 2 groups: monotherapy (MT) with VKA (n = 101) or multiple antithrombotic therapy (MAT) with VKA plus 1 or 2 antiplatelet agents (aspirin or clopidogrel; n = 520). Endpoint definitions were in accordance with Valve Academic Research Consortium-2 criteria. The rate of stroke, major adverse cardiovascular events (stroke, myocardial infarction, or cardiovascular death), major or life-threatening bleeding events, and death were assessed by a Cox multivariate model regression survival analysis according to the antithrombotic regime used.RESULTS During a median follow-up of 13 months (interquartile range: 3 to 31 months) there were no differences between groups in the rate of stroke (MT: 5%, MAT: 5.2%; adjusted hazard ratio [HR]: 1.25; 95% confidence interval [CI]: 0.45 to 3.48; p = 0.67), major adverse cardiovascular events (MT: 13.9%, MAT: 16.3%; adjusted HR: 1.33; 95% CI: 0.75 to 2.36; p = 0.33), and death (MT 22.8%, MAT: 19.2%; adjusted HR: 0.93; 95% CI: 0.58 to 1.50; p = 0.76). A higher risk of major or life-threatening bleeding was found in the MAT group (MT: 14.9%, MAT: 24.4%; adjusted HR: 1.85; 95% CI: 1.05 to 3.28; p = 0.04). These results remained similar when patients receiving VKA plus only 1 antiplatelet agent (n = 463) were evaluated.CONCLUSIONS In TAVR recipients prescribed VKA therapy for AF, concomitant antiplatelet therapy use appears not to reduce the incidence of stroke, major adverse cardiovascular events, or death, while increasing the risk of major or life-threatening bleeding. (C) 2016 by the American College of Cardiology Foundation.

Made available in DSpace on 2021-06-25T12:20:30Z (GMT). No. of bitstreams: 0 Previous issue date: 2020-10-01 Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) Many diseases of the respiratory system occur differently in males and females, indicating a possible role of gonadal hormones in respiratory control. We hypothesized that testosterone (T) is important for the ventilatory chemosensitivity responses in males. To test this hypothesis, we evaluated ventilation ((E)), metabolic rate and body temperature (T-b) under normoxia/normocapnia, hypercapnia and hypoxia in orchiectomized (ORX), ORX with testosterone replacement (ORX + T) or flutamide (FL, androgen receptor blocker)-treated rats. We also performed immunohistochemistry to evaluate the presence of androgen receptor (AR) in the carotid body ( CB) of intact males. Orchiectomy promoted a reduction (E) and ventilatory equivalent ((E)/O-2) under room-air conditions, which was restored with testosterone treatment. Moreover, during hypoxia or hypercapnia, animals that received testosterone replacement had a higher (E) and (E)/O-2 than control and ORX, without changes in metabolic and thermal variables. Flutamide decreased the hypoxic ventilatory response without changing the CO2-drive to breathe, suggesting that the testosterone effect on hypercapnic hyperventilation does not appear to involve the AR. We also determined the presence of AR in the CB of intact animals. Our findings demonstrate that testosterone seems to be important for maintaining resting (E) in males. In addition, the influence of testosterone on (E), either during resting conditions or under hypoxia and hypercapnia, seems to be a direct and specific effect, as no changes in metabolic rate or T-b were observed during any treatment. Finally, a putative site of testosterone action during hypoxia is the CB, since we detected the presence of AR in this structure. Sao Paulo State Univ, Fac Agr & Veterinarian Sci, Dept Anim Morphol & Physiol, Jaboticabal, SP, Brazil St Michaels Hosp, Brain & Breathing Sci Lab, Keenan Res Ctr Biomed Sci, Toronto, ON, Canada Fed Univ Minas Gerais UFMG, Inst Biol Sci, Dept Physiol & Biophys, Belo Horizonte, MG, Brazil Sao Paulo State Univ, Fac Agr & Veterinarian Sci, Dept Anim Morphol & Physiol, Jaboticabal, SP, Brazil FAPESP: 2019/09469-8 CNPq: CNPq -407490/2018-3 FAPESP: 2016/04276-9 CNPq: 140715/2015-0

Made available in DSpace on 2018-11-26T15:43:53Z (GMT). No. of bitstreams: 0 Previous issue date: 2017-03-01 Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) Infectious pneumonia is a major cause of morbidity/mortality, mainly because of the increasing rate of microorganisms resistant to antibiotics. Photodynamic Therapy (PDT) is emerging as a promising approach, as effects are based on oxidative stress, preventing microorganism resistance. In two previous studies, the in vitro inactivation of Streptococcus pneumoniae using indocyanine green (ICG) and infrared light source was a success killing 5 log10 colony-forming units (CFU/mL) with only 10 lmol/L ICG. In this work, a proof-of-principle protocol was designed to treat lung infections by PDT using extracorporeal illumination with a 780 nm laser device and also ICG as photosensitizer. Hairless mice were infected with S. pneumoniae and PDT was performed two days after infection. For control groups, CFU recovery ranged between 10(3)-10(4) / mouse. For PDT group, however, no bacteria were recovered in 80% of the animals. Based on this result, animal survival was evaluated separately over 50 days. No deaths occurred in PDT group, whereas 60% of the control group died. Our results indicate that extracorporeal PDT has the potential for pneumonia treatment, and pulmonary decontamination with PDT may be used as a single therapy or as an antibiotics adjuvant. Univ Sao Paulo, Sao Carlos, SP, Brazil Univ Fed Sao Carlos, Sao Carlos, SP, Brazil Sao Paulo State Univ, Araraquara, Brazil St Michaels Hosp, Keenan Res Ctr, Toronto, ON, Canada Sao Paulo State Univ, Araraquara, Brazil FAPESP: 13/07276-1 CAPES: 99999.003154/2015-07