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J Exp Med ; 216(9): 2038-2056, 2019 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-31217193


Autosomal recessive IRF7 and IRF9 deficiencies impair type I and III IFN immunity and underlie severe influenza pneumonitis. We report three unrelated children with influenza A virus (IAV) infection manifesting as acute respiratory distress syndrome (IAV-ARDS), heterozygous for rare TLR3 variants (P554S in two patients and P680L in the third) causing autosomal dominant (AD) TLR3 deficiency. AD TLR3 deficiency can underlie herpes simplex virus-1 (HSV-1) encephalitis (HSE) by impairing cortical neuron-intrinsic type I IFN immunity to HSV-1. TLR3-mutated leukocytes produce normal levels of IFNs in response to IAV. In contrast, TLR3-mutated fibroblasts produce lower levels of IFN-ß and -λ, and display enhanced viral susceptibility, upon IAV infection. Moreover, the patients' iPSC-derived pulmonary epithelial cells (PECs) are susceptible to IAV. Treatment with IFN-α2b or IFN-λ1 rescues this phenotype. AD TLR3 deficiency may thus underlie IAV-ARDS by impairing TLR3-dependent, type I and/or III IFN-mediated, PEC-intrinsic immunity. Its clinical penetrance is incomplete for both IAV-ARDS and HSE, consistent with their typically sporadic nature.

Br J Clin Pharmacol ; 69(2): 136-42, 2010 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-20233176


AIMS: " Arnica montana is a popular homoeopathic treatment with potential haemostatic and anti-inflammatory properties. A homoeopathic combination of A. montana and Bryonia alba was used in aortic valve surgery to evaluate its effectiveness in reducing bleeding, inflammation, pain and myocardial ischaemia. METHODS: One day before surgery, 92 adult patients were randomly assigned to a double-blind parallel trial with either homoeopathic granules or a matching placebo until 4 days after surgery. The primary outcome was the volume of blood/liquid in the drains at their removal. The secondary outcomes included postoperative blood/liquid losses at 12 and 24 h as well as C-reactive protein (CRP), pain, temperature and plasma troponin Ic. RESULTS: At 12 h and 24 h after surgery, then at drain removal, blood losses in homoeopathy and placebo groups were not statistically significant (362 +/- 218, 520 +/- 269 and 640 +/- 297 ml vs. 456 +/- 440, 620 +/- 477 and 796 +/- 717 ml; P= 0.19, 0.23 and 0.35, respectively). The statistical modelling did not show significantly different patterns of CRP, troponin and body temperature changes or of pain perception. The number of transfused packed red cells was not significantly different either (P= 0.58). Two patients from each group died during the study period and the number of serious adverse events was not statistically different (six in homoeopathy vs. 10 in placebo groups; Fisher's exact test P= 0.41). CONCLUSIONS: In the study setting, there was no evidence of effects of A. montana and B. alba combination on bleeding, inflammation, pain or myocardial ischaemia.

Arnica , Bryonia , Hemorragia/tratamento farmacológico , Homeopatia/métodos , Inflamação/tratamento farmacológico , Isquemia Miocárdica/tratamento farmacológico , Extratos Vegetais/uso terapêutico , Complicações Pós-Operatórias/tratamento farmacológico , Idoso , Idoso de 80 Anos ou mais , Valva Aórtica/cirurgia , Procedimentos Cirúrgicos Cardíacos/métodos , Método Duplo-Cego , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Dor Pós-Operatória/tratamento farmacológico , Fitoterapia , Hemorragia Pós-Operatória/tratamento farmacológico , Análise de Regressão , Resultado do Tratamento
Anesth Analg ; 104(5): 1059-65, tables of contents, 2007 May.
Artigo em Inglês | MEDLINE | ID: mdl-17456653


BACKGROUND: Plasma B-type natriuretic peptide (BNP) can predict postoperative complications after cardiac surgery in adults. Our aim was to investigate BNP kinetics and prognostic value in neonates undergoing the arterial switch operation (ASO) for transposition of the great arteries (TGA). METHODS: We measured BNP concentrations in 30 neonates before, immediately after, and 6, 12, 24, and 48 h after ASO for TGA. Complicated postoperative evolution was defined as patients requiring mechanical ventilation or presenting low cardiac output syndrome for more than 72 h. We studied the ability of postoperative BNP concentrations to predict complicated evolution. RESULTS: Intubation duration, inotropic support duration, and intensive care unit stay were 68 (48-121) h, 78 (69-141) h, and 96 (76-149) h respectively. Patients with complicated evolution had higher 6 and 12-h BNP concentrations than patients with simple evolution (459 (210-897) vs 137 (67-248) ng/L and 547 (193-868) vs 185 (79-354) ng/L respectively; P < 0.05) and had longer intubation, inotropic support, and intensive care unit stay (96 (70-190) vs 50 (48-66) h, 100 (83-190) vs 70 (59-72) h, and 120 (90-240) vs 84 (72-96) h, P < 0.05). A 6-h BNP concentration >160 ng/L was able to predict complicated evolution with a sensitivity of 93% and a specificity of 67%. CONCLUSION: In neonates, BNP concentrations can predict adverse outcome in the postoperative period after ASO for TGA. This marker has potential clinical applications.

Procedimentos Cirúrgicos Cardiovasculares , Peptídeo Natriurético Encefálico/sangue , Complicações Pós-Operatórias/sangue , Complicações Pós-Operatórias/diagnóstico , Biomarcadores/sangue , Feminino , Humanos , Recém-Nascido , Masculino , Prognóstico , Estudos Prospectivos , Fatores de Tempo
J Thorac Cardiovasc Surg ; 130(3): 803-9, 2005 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-16153932


BACKGROUND: A simplified alternative to the Cox maze procedure to treat atrial fibrillation with epicardial high-intensity focused ultrasound was evaluated clinically, and the initial clinical results were assessed at the 6-month follow-up visit. METHODS: From September 2002 through February 2004, 103 patients were prospectively enrolled in a multicenter study. Atrial fibrillation duration ranged from 6 to 240 months (mean, 44 months) and was permanent in 76 (74%) patients, paroxysmal in 22 (21%) patients, and persistent in 5 (5%) patients. All patients had concomitant operations, and ablation was performed epicardially on the beating heart before the concomitant procedure. The device automatically created a circumferential left atrial ablation around the pulmonary veins in an average of 10 minutes, and an additional mitral line was created epicardially in 35 (34%) patients with a handheld device by using the same technology. RESULTS: No complications or deaths were device or procedure related. There were 4 (3.8%) early deaths and 2 late extracardiac deaths. The 6-month follow-up was complete in all survivors. At the 6-month visit, freedom from atrial fibrillation was 85% in the entire study group (80% in patients with permanent atrial fibrillation, 88% in the 35 patients who had the additional mitral line, and 100% in patients with paroxysmal atrial fibrillation). A pacemaker was implanted in 8 patients. Only the duration and type of atrial fibrillation significantly increased the risk of recurrence. CONCLUSION: Epicardial, off-pump, beating-heart ablation with acoustic energy is safe and cures 80% of patients with permanent atrial fibrillation associated with long-standing structural heart disease.

Fibrilação Atrial/cirurgia , Terapia por Ultrassom , Adulto , Idoso , Procedimentos Cirúrgicos Cardíacos/instrumentação , Procedimentos Cirúrgicos Cardíacos/métodos , Estudos de Viabilidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento , Terapia por Ultrassom/efeitos adversos , Terapia por Ultrassom/instrumentação , Terapia por Ultrassom/métodos