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1.
JAMA Netw Open ; 7(3): e241537, 2024 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-38451520

RESUMO

Importance: New-onset postoperative atrial fibrillation (POAF) occurs in approximately 30% of patients undergoing coronary artery bypass grafting (CABG). It is unknown whether early recurrence is associated with worse outcomes. Objective: To test the hypothesis that early AF recurrence in patients with POAF after CABG is associated with worse outcomes. Design, Setting, and Participants: This Swedish nationwide cohort study used prospectively collected data from the SWEDEHEART (Swedish Web System for Enhancement and Development of Evidence-Based Care in Heart Disease Evaluated According to Recommended Therapies) registry and 3 other mandatory national registries. The study included patients who underwent isolated first-time CABG between January 1, 2007, and December 31, 2020, and developed POAF. Data analysis was performed between March 6 and September 16, 2023. Exposure: Early AF recurrence defined as an episode of AF leading to hospital care within 3 months after discharge. Main Outcomes and Measures: The primary outcome was all-cause mortality. Secondary outcomes included ischemic stroke, any thromboembolism, heart failure hospitalization, and major bleeding within 2 years after discharge. The groups were compared with multivariable Cox regression models, with early AF recurrence as a time-dependent covariate. The hypothesis tested was formulated after data collection. Results: Of the 35 329 patients identified, 10 609 (30.0%) developed POAF after CABG and were included in this study. Their median age was 71 (IQR, 66-76) years. The median follow-up was 7.1 (IQR, 2.9-9.0) years, and most patients (81.6%) were men. Early AF recurrence occurred in 6.7% of patients. Event rates (95% CIs) per 100 patient-years with vs without early AF recurrence were 2.21 (1.49-3.24) vs 2.03 (1.83-2.25) for all-cause mortality, 3.94 (2.92-5.28) vs 2.79 (2.56-3.05) for heart failure hospitalization, and 3.97 (2.95-5.30) vs 2.74 (2.51-2.99) for major bleeding. No association between early AF recurrence and all-cause mortality was observed (adjusted hazard ratio [AHR], 1.17 [95% CI, 0.80-1.74]; P = .41). In exploratory analyses, there was an association with heart failure hospitalization (AHR, 1.80 [95% CI, 1.32-2.45]; P = .001) and major bleeding (AHR, 1.92 [1.42-2.61]; P < .001). Conclusions and Relevance: In this cohort study of early AF recurrence after POAF in patients who underwent CABG, no association was found between early AF recurrence and all-cause mortality. Exploratory analyses showed associations between AF recurrence and heart failure hospitalization, oral anticoagulation, and major bleeding.


Assuntos
Fibrilação Atrial , Insuficiência Cardíaca , Masculino , Humanos , Idoso , Feminino , Fibrilação Atrial/epidemiologia , Fibrilação Atrial/etiologia , Estudos de Coortes , Insuficiência Cardíaca/epidemiologia , Insuficiência Cardíaca/etiologia , Ponte de Artéria Coronária/efeitos adversos , Hemorragia
2.
J Clin Med ; 12(23)2023 Nov 29.
Artigo em Inglês | MEDLINE | ID: mdl-38068441

RESUMO

When using rapid deployment surgical aortic valve replacement (RD SAVR) in treating bicuspid aortic valve morphology (BAV), several challenges are faced due to annular asymmetry. The Sievers classification has been traditionally used for the description of BAV morphology. In this study, we aimed to conduct a retrospective feasibility analysis of RD SAVR in relation to the Sievers classification. From January 2014 to March 2022, 31 patients with BAV morphology (15 patients with Sievers type 0 BAV and 16 with Sievers type 1 BAV) underwent RD SAVR. Specific surgical techniques were applied depending on the BAV morphology. Comparable clinical outcomes were observed. No paravalvular leaks and no valvular re-interventions occurred in either group. CPB and cross-clamping times, as well as the prosthesis sizes used, were also not significantly different. Postoperative mean gradients were comparable in both groups. No significant distinction was found between the groups in terms of postoperative pacemaker indication, postoperative stroke, or death. Annular symmetry can be adequately restored through precise prosthesis sizing and placement according to an individual's valve morphology regardless of the Sievers classification of BAV by choosing a different landmark for the initial suture. RD SAVR seems to be a safe approach for any bicuspid morphology, with good hemodynamic results and time-saving potential in experienced hands.

3.
Nutrients ; 15(4)2023 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-36839210

RESUMO

There is scarce evidence about early nutrition programming of dynamic aspects of glucose homeostasis. We analyzed the long-term effects of early nutrition on glycemic variability in healthy children. A total of 92 children participating in the COGNIS study were considered for this analysis, who were fed with: a standard infant formula (SF, n = 32), an experimental formula (EF, n = 32), supplemented with milk fat globule membrane (MFGM) components, long-chain polyunsaturated fatty acids (LC-PUFAs), and synbiotics, or were breastfed (BF, n = 28). At 6 years old, BF children had lower mean glucose levels and higher multiscale sample entropy (MSE) compared to those fed with SF. No differences in MSE were found between EF and BF groups. Normal and slow weight gain velocity during the first 6 months of life were associated with higher MSE at 6 years, suggesting an early programming effect against later metabolic disorders, thus similarly to what we observed in breastfed children. Conclusion: According to our results, BF and normal/slow weight gain velocity during early life seem to protect against glucose homeostasis dysregulation at 6 years old. EF shows functional similarities to BF regarding children's glucose variability. The detection of glucose dysregulation in healthy children would help to develop strategies to prevent the onset of metabolic disorders in adulthood.


Assuntos
Fórmulas Infantis , Leite Humano , Lactente , Feminino , Humanos , Criança , Fórmulas Infantis/análise , Seguimentos , Aleitamento Materno , Ácidos Graxos , Aumento de Peso , Homeostase
4.
Front Nutr ; 9: 935740, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36313089

RESUMO

Breastfeeding (BF) is the gold standard in infant nutrition; knowing how it influences brain connectivity would help understand the mechanisms involved, which would help close the nutritional gap between infant formulas and breast milk. We analyzed potential long-term differences depending on the diet with an experimental infant formula (EF), compared to a standard infant formula (SF) or breastfeeding (BF) during the first 18 months of life on children's hypothalamic functional connectivity (FC) assessed at 6 years old. A total of 62 children participating in the COGNIS randomized clinical trial (Clinical Trial Registration: www.ClinicalTrials.gov, identifier: NCT02094547) were included in this study. They were randomized to receive an SF (n = 22) or a bioactive nutrient-enriched EF (n = 20). BF children were also included as a control study group (BF: n = 20). Brain function was evaluated using functional magnetic resonance imaging (fMRI) and mean glucose levels were collected through a 24-h continuous glucose monitoring (CGM) device at 6 years old. Furthermore, nutrient intake was also analyzed during the first 18 months of life and at 6 years old through 3-day dietary intake records. Groups fed with EF and BF showed lower FC between the medial hypothalamus (MH) and the anterior cingulate cortex (ACC) in comparison with SF-fed children. Moreover, the BF children group showed lower FC between the MH and the left putamen extending to the middle insula, and higher FC between the MH and the inferior frontal gyrus (IFG) compared to the EF-fed children group. These areas are key regions within the salience network, which is involved in processing salience stimuli, eating motivation, and hedonic-driven desire to consume food. Indeed, current higher connectivity found on the MH-IFG network in the BF group was associated with lower simple sugars acceptable macronutrient distribution ranges (AMDRs) at 6 months of age. Regarding linoleic acid intake at 12 months old, a negative association with this network (MH-IFG) only in the BF group was found. In addition, BF children showed lower mean glucose levels compared to SF-fed children at 6 years old. Our results may point out a possible relationship between diet during the first 18 months of life and inclined proclivity for hedonic eating later in life. Clinical trial registration: https://www.clinicaltrials.gov/, identifier NCT02094547.

5.
Clin Nutr ; 41(8): 1697-1711, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-35777109

RESUMO

BACKGROUND & AIMS: The critical window of concurrent developmental paths of the nervous system and gut microbiota in infancy provides an opportunity for nutritional interventions with potential health benefits later in life. METHODS: We compared the dynamics of gut microbiota maturation and explored its association with neurodevelopment at 12 months and 4 years of age in 170 full-term healthy infants fed a standard formula (SF) or a new formula (EF) based on standard formula supplemented with synbiotics, long chain polyunsaturated fatty acids (LC-PUFA) and bovine milk fat globule membranes (MFGM), including a breastfed reference group (BF). RESULTS: Using Dirichlet Multinomial Modelling, we characterized three microbial enterotypes (Mixed, anaerobic and aerobic profile; Bact, Bacteroides-dominant; Firm, Firmicutes-enriched) and identified a new enterotype dominated by an unidentified genus within Lachnospiraceae (U_Lach). Enterotypes were associated with age (Mixed with baseline, U_Lach with month 6, Bact and Firm with months 12 and 18). Trajectories or timely enterotype shifts in each infant were not random but strongly associated with type of feeding. Trajectories in SF shifted from initial Mixed to U_Lach, Bact or Firm at month. Microbiota maturation in EF split into a fast trajectory as in SF, and a slow trajectory with Mixed to U_Lach, Bact or Firm transitions at months 12 or 18, as in BF. EF infants with slow trajectories were more often in-home reared and born by vaginal delivery to mothers with pre-pregnancy lean BMI. At 12 months of age, language and expressive language scores were significantly higher in EF infants with fast trajectories than in BF. Neurodevelopmental outcomes were similar between EF infants with slow trajectories and BF at 12 months and 4 years of age. CONCLUSIONS: Feeding a synbiotics, LC-PUFA and MFGM supplemented formula in a specific infant environment promoted probiotic growth and retarded gut microbiota maturation with similar neurodevelopment outcomes to breastfed infants. CLINICAL TRIAL REGISTRY NUMBER: NCT02094547.


Assuntos
Microbiota , Simbióticos , Aleitamento Materno , Ácidos Graxos , Ácidos Graxos Insaturados , Feminino , Glicolipídeos , Glicoproteínas , Humanos , Lactente , Fórmulas Infantis , Gotículas Lipídicas
6.
Front Nutr ; 9: 820224, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35356726

RESUMO

Background: Adequate nutrient intake during the first few months of life plays a critical role on brain structure and function development. Objectives: To analyze the long-term effects of an experimental infant formula (EF) on neurocognitive function and brain structure in healthy children aged 6 years compared to those fed with a standard infant formula or breastfed. Methods: The current study involved 108 healthy children aged 6 years and participating in the COGNIS Study. At 0-2 months, infants were randomized to receive up to 18 months of life a standard infant formula (SF) or EF enriched with milk fat globule membrane (MFGM), long-chain polyunsaturated fatty acids (LC-PUFAs) and synbiotics. Furthermore, a reference group of breastfed (BF) infants were also recruited. Children were assessed using neurocognitive tests and structural Magnetic Resonance Imaging (MRI) at 6 years old. Results: Experimental infant formula (EF) children showed greater volumes in the left orbital cortex, higher vocabulary scores and IQ, and better performance in an attention task than BF children. EF children also presented greater volumes in parietal regions than SF kids. Additionally, greater cortical thickness in the insular, parietal, and temporal areas were found in children from the EF group than those fed with SF or BF groups. Further correlation analyses suggest that higher volumes and cortical thickness of different parietal and frontal regions are associated with better cognitive development in terms of language (verbal comprehension) and executive function (working memory). Finally, arachidonic acid (ARA), adrenic acid (AdA), docosahexaenoic acid (DHA) levels in cheek cell glycerophospholipids, ARA/DHA ratio, and protein, fatty acid, and mineral intake during the first 18 months of life seem to be associated with changes in the brain structures at 6 years old. Conclusions: Supplemented infant formula with MFGM components, LC-PUFAs, and synbiotics seems to be associated to long-term effects on neurocognitive development and brain structure in children at 6 years old. Clinical Trial Registration: https://www.clinicaltrials.gov/, identifier: NCT02094547.

7.
Eur J Cardiothorac Surg ; 61(5): 1109-1115, 2022 05 02.
Artigo em Inglês | MEDLINE | ID: mdl-35076056

RESUMO

OBJECTIVES: The aim of this study was to evaluate the surgical outcome of patients suffering from native aortic valve (NVE) or prosthetic aortic valve endocarditis (PVE) treated with the EDWARDS INTUITY Elite rapid-deployment valve prosthesis. METHODS: Between February 2019 and June 2020, 25 patients suffering from NVE (n = 9; 36%) and PVE (n = 16; 64%) of the aortic valve received an INTUITY valve at our institution. Preoperative, operative and follow-up data were collected. RESULTS: In our cohort, the mean EuroSCORE II was 13.4%. Eleven patients (44%) received concomitant aortic root patch plasty. Four patients (16%) received coronary artery bypass graft surgery, 3 patients (12%) received mitral valve repair and 2 patients (8%) underwent replacement of the ascending aorta. The cardiopulmonary bypass and aortic cross-clamp times were 124 ± 56 and 75 ± 39 min, respectively. The mean intensive care unit stay was 5 days. The mean size of the implanted prostheses was 25 ± 2 mm and the mean prosthesis transvalvular gradient 3 months after surgery was 9 ± 4 mmHg. During follow-up, no case of recurrent endocarditis occurred, 1 patient died of multisystem organ failure which had already been present preoperatively. CONCLUSIONS: Surgery for NVE and PVE of the aortic valve may be safely performed using the EDWARDS INTUITY Elite valve system. This procedure could be well implemented in cases with extensive infection, fragile root tissue and root abscesses requiring root reconstruction. In our institution, the rapid-deployment aortic valve replacement strategy has become an important tool in the armamentarium of the surgical endocarditis treatment.


Assuntos
Estenose da Valva Aórtica , Endocardite Bacteriana , Endocardite , Implante de Prótese de Valva Cardíaca , Próteses Valvulares Cardíacas , Valva Aórtica/cirurgia , Estenose da Valva Aórtica/cirurgia , Endocardite/cirurgia , Endocardite Bacteriana/cirurgia , Próteses Valvulares Cardíacas/efeitos adversos , Implante de Prótese de Valva Cardíaca/efeitos adversos , Implante de Prótese de Valva Cardíaca/métodos , Humanos , Resultado do Tratamento
8.
Anal Bioanal Chem ; 414(3): 1217-1225, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34240229

RESUMO

High per- and polyfluorinated alkyl substance (PFAS) concentrations have been detected in agricultural soils in Southwest Germany. Discharges of PFAS-contaminated paper sludge and compost are suspected to be the cause of the contamination. Perfluorinated carboxylic acids (PFCAs) have been detected also in groundwater, drinking water, and plants in this area. Recently, previously unknown compounds have been identified by high-resolution mass spectrometry (HRMS). Major contaminants were polyfluorinated dialkylated phosphate esters (diPAPs) and N-ethyl perfluorooctane sulfonamide ethanol-based phosphate diester (diSAmPAP). In this study, HRMS screening for PFAS was applied to 14 soil samples from the contaminated area and 14 impregnated paper samples which were from a similar period than the contamination. The paper samples were characterized by diPAPs (from 4:2/6:2 to 12:2/12:2), fluorotelomer mercapto alkyl phosphates (FTMAPs; 6:2/6:2 to 10:2/10:2), and diSAmPAP. In soil samples, diPAPs and their transformation products (TPs) were the major contaminants, but also FTMAPs, diSAmPAP, and their TPs occurred. The distribution patterns of the carbon chain lengths of the precursor PFAS in soil samples were shown to resemble those in paper samples. This supports the hypothesis that paper sludge is a major source of contamination. The presence of major degradation products like PFCAs, FTSAs, or PFOS and their distribution of carbon chain lengths indicate the activity of biotic or abiotic degradation processes and selective leaching processes from the upper soil horizons.

9.
J Cardiovasc Electrophysiol ; 32(8): 2171-2178, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34164884

RESUMO

INTRODUCTION: Cardiac surgery may influence occurrence and persistence of atrial fibrillation (AF). In patients with a history of cardiac surgery and postoperative pacemaker or implantable cardioverter defibrillator implantation we attempted to quantify AF characteristics and investigate factors that influence AF recurrence. METHODS: In 426 patients (319 male; age: 73 SD: 9 years) with a history of cardiac surgery (364 CABG; 69 mitral valve; 57 aortic valve and 59 combination procedures) the heart rhythm history (mean: 351 days SD: 54 days) was reconstructed and investigated for AF recurrence patterns. RESULTS: AF developed and subsequently recurred in 75% of patients (n = 320). The mean AF burden in these patients was 0.21 (21% of the total observed time spent in AF) and 4085 episodes of AF were observed and analyzed. AF episodes spontaneously terminated within 24 h (n = 2509), 48 h (n = 700), 72 h (n = 279), and 1 week (n = 31). The probability of spontaneous conversion to sinus rhythm (SR) decreased with time spent in AF and plateaued after approximately 7 days. Patient age, LVEF and presence of coronary artery disease significantly influenced the probability of spontaneous conversion to SR. Type of cardiac surgery also significantly influenced AF episode characteristics. CONCLUSION: AF episodes are common in patients with a history of cardiac surgery. Spontaneous conversion to SR diminishes with increasing time spent in AF and is influenced by AF characteristics and several patient-related factors. Continuous monitoring can provide detailed information about AF recurrence that may immensely improve our understanding and influence the clinical management of AF.


Assuntos
Fibrilação Atrial , Procedimentos Cirúrgicos Cardíacos , Marca-Passo Artificial , Idoso , Fibrilação Atrial/diagnóstico , Fibrilação Atrial/cirurgia , Humanos , Masculino , Valva Mitral , Recidiva , Resultado do Tratamento
10.
Br J Nutr ; 126(12): 1809-1822, 2021 12 28.
Artigo em Inglês | MEDLINE | ID: mdl-33602357

RESUMO

Type of feeding during early life influences growth trajectory and metabolic risk at later ages. Modifications in infant formula composition have led to evaluate their effects on growth and energetic efficiency (EE) compared with breast-feeding. Main goal was to analyse type of feeding potential effects during first months of life, plus its EE, on growth patterns in healthy formula fed (standard infant formula (SF) vs. experimental infant formula enriched with bioactive nutrients (EF)) and breastfed (BF) infants participating in the COGNIS RCT (http://www.ClinicalTrials.gov, Identifier: NCT02094547) up to 18 months of age. Infants follow-up to 18 months of age (n 141) fed with a SF (n 48), EF(n 56), or BF (n 37), were assessed for growth parameters using WHO standards. Growth velocity (GV) and catch-up were calculated to identify growth patterns. EE of breast milk/infant formula was also estimated. Infants' growth at 6 months showed higher length and lower head circumference gains in SF and EF infants than BF infants. Both weight-for-length and weight-for-age catch-up growth showed significant differences in formula fed groups compared with the BF. No significant differences in GV or catch-up were found at 6-12 and 12-18 months. Regarding EE, infant formula groups showed significantly lower weight and length gains/g of milk protein, and higher weight and length gains/g of milk lipids, than the BF infants. GV during first 6 months, which may be influenced by feeding, seems to be the main predictor of subsequent growth trajectory. Breast-feeding may have positive effects on growth programming due to its nutrients' EE.


Assuntos
Fórmulas Infantis , Leite Humano , Aleitamento Materno , Feminino , Humanos , Lactente , Nutrientes
11.
J Cardiovasc Electrophysiol ; 32(4): 1103-1110, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33566390

RESUMO

INTRODUCTION: Mitral valve surgery has developed into a strong subspecialty of cardiac surgery with operative techniques and outcomes constantly improving. The development of bradyarrhythmias after mitral valve surgery is not completely understood. METHODS: We investigated a cohort of 797 patients requiring mitral valve surgery with and without concomitant procedures. Incidences and predictors of pacemaker requirement as well as survival were analyzed. RESULTS: In the complete follow-up period (median follow-up time: 6.09 years [95% confidence interval [CI]: 5.94-6.22 years, maximum 8.77 years) 80 patients (10% of the complete cohort) required pacemaker implantation for bradyarrhythmia. The cumulative rate of pacemaker implantation was 6.4% at 50 days (48 patients) with most (54.2%) requiring pacing for atrioventricular block. Mitral valve replacement (odds ratio [OR]: 1.905; 95% CI: 1.206-3.536; p = .041) and tricuspid ring annuloplasty (OR: 2.348; 95% CI: 1.165-4.730, p = .017) were identified as operative risk factors of pacemaker requirement after mitral valve surgery. Insulin-dependent diabetes mellitus was also identified as a predictor of pacemaker requirement (OR: 4.665; 95% CI: 1.975-11.02; p = .001). There was no difference in survival in the paced and unpaced groups. CONCLUSIONS: After mitral valve surgery, a relevant subgroup of patients requires pacemaker implantation-most for atrioventricular block. We identified mitral valve replacement and tricuspid ring annuloplasty as significant operative risk factors and insulin-dependent diabetes mellitus as a demographic risk factor. While anatomic relationships help explain the operative risk factors the role of diabetes mellitus is not completely understood.


Assuntos
Implante de Prótese de Valva Cardíaca , Anuloplastia da Valva Mitral , Bradicardia , Implante de Prótese de Valva Cardíaca/efeitos adversos , Humanos , Valva Mitral/diagnóstico por imagem , Valva Mitral/cirurgia , Estudos Retrospectivos , Fatores de Tempo , Resultado do Tratamento , Valva Tricúspide/cirurgia
12.
Int Heart J ; 62(1): 57-64, 2021 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-33455981

RESUMO

Tricuspid valve (TV) surgery is associated with a high risk of postoperative pacemaker requirement. We set out to identify the incidence of atrioventricular block (AVB) after TV surgery and determine whether atrioventricular conduction recovers within time.We investigated pre/intra- and postoperative predictors of AVB in patients who underwent tricuspid valve surgery (not only isolated TV surgery) at our institution between 2004 and 2017. Patients who had pacemakers prior to surgery were excluded.One year after surgery, 5.8% of the surviving cohort had received a pacemaker due to AVB. In the complete follow-up time, 33 out of 505 patients required pacemaker implantation because of AVB. Of the 37 patients who presented to the intensive care unit postoperatively with AVB III, 14 (38%) underwent pacemaker implantation for AVB, and 20 (54%) did not require a pacemaker. AVB III at ICU admission was identified as a predictor of pacemaker implantation (OR: 9.7, CI: 3.8-24.5, P < 0.001). TV endocarditis was also identified as a predictor (OR: 12.4, CI: 3.3-46.3, P < 0.001). Eleven out of 32 patients (34%) with tricuspid endocarditis required a pacemaker for AVB. The mean ventricular pacing burden within the first 5 years after pacemaker implantation was 79%.The issue of AVB after TV surgery is significant. Both the initial rhythm after surgery and etiology of the tricuspid disease can help predict pacemaker requirement. Within the first 5 years after surgery, the ventricular pacing burden remains high without relevant rhythm recovery.


Assuntos
Bloqueio Atrioventricular/etiologia , Endocardite/complicações , Marca-Passo Artificial/estatística & dados numéricos , Valva Tricúspide/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Bloqueio Atrioventricular/fisiopatologia , Bloqueio Atrioventricular/cirurgia , Intervalo Livre de Doença , Endocardite/cirurgia , Feminino , Seguimentos , Doenças das Valvas Cardíacas/complicações , Doenças das Valvas Cardíacas/patologia , Humanos , Unidades de Terapia Intensiva/estatística & dados numéricos , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/fisiopatologia , Estudos Retrospectivos , Fatores de Risco , Valva Tricúspide/patologia
13.
mBio ; 13(1): e0383321, 2021 02 22.
Artigo em Inglês | MEDLINE | ID: mdl-35164566

RESUMO

Rhodomyrtone (Rom) is a plant-derived broad-spectrum antibiotic active against many Gram-positive pathogens. A single point mutation in the regulatory farR gene (farR*) confers resistance to Rom in Staphylococcus aureus (RomR). The mutation in farR* alters the activity of the regulator, FarR*, in such a way that not only its own gene, farR*, but also the divergently transcribed farE gene and genes controlled by the global regulator, agr, are highly upregulated. Here, we show that mainly the upregulation of the fatty acid efflux pump FarE causes the RomR phenotype, as farE deletion in either the parent or the RomR strain (RomR ΔfarE) yielded hypersensitivity to Rom. Comparative lipidome analysis of the supernatant (exolipidomics) and the pellet fraction revealed that the RomR strain excreted about 10 times more phospholipids (PGs) than the parent strain or the ΔfarE mutants. Since the PG content in the supernatant (2,244 ng/optical density [OD]) was more than 100-fold higher than that of fatty acids (FA), we assumed that PG interacts with Rom, thereby abrogating its antimicrobial activity. Indeed, by static and dynamic light scattering (SLS and DLS) and isothermal titration calorimetry (ITC) analyses, we could demonstrate that both PG and Rom were vesicular and reacted with each other in milliseconds to form a 1:1.49 [Rom-PG(32:0), where PG(32:0) is PG with C32:0 lipids] complex. The binding is entropically driven and hence hydrophobic and of low specificity in nature. Our results indicate that the cytoplasmic membrane is the actual target of Rom, which is also in agreement with Rom's induced rapid collapse of the membrane potential and decreased membrane integrity. IMPORTANCE Antibiotic resistance is a growing public health problem, and alternative antibiotics are urgently needed. Rhodomyrtone (Rom), an antimicrobial compound originally isolated from Rhodomyrtus tomentosa, is active against multidrug-resistant Gram-positive pathogens. However, Rom-resistant (RomR) mutants occur with low frequency. In this study, we unraveled the underlying resistance mechanism, which is based on a point mutation in the farR regulator gene, causing overexpression of FarE, which most likely acts as a phospholipid (PG) efflux pump, as large amounts of PG were found in the supernatant and the pellet fraction. We show that PG can bind to Rom, thereby abrogating its antimicrobial activity. The direct interaction of Rom with PG suggests that Rom's actual target is the cytoplasmic membrane. Antibiotics that interact with PG are rare. Since Rom can be chemically synthesized, it serves as a lead compound for synthesis of improved variants.


Assuntos
Antibacterianos , Anti-Infecciosos , Farmacorresistência Bacteriana , Staphylococcus aureus , Xantonas , Antibacterianos/farmacologia , Anti-Infecciosos/metabolismo , Proteínas de Bactérias/metabolismo , Testes de Sensibilidade Microbiana , Staphylococcus aureus/genética , Xantonas/metabolismo , Farmacorresistência Bacteriana/genética
14.
Nutrients ; 12(12)2020 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-33333767

RESUMO

Although early life nutrition influences brain development and mental health, the long-term effects of supplemented infant formula on children´s behavior remain unclear. We analyzed the effects of a bioactive nutrients-enriched-infant formula on children's behavior up to 2.5 years, compared to a standard infant formula or breastfeeding. Current analysis involved 70 children who were fed a standard infant formula (SF, n = 29) or a bioactive compounds enriched-infant formula (EF, n = 41), during their first 18 months of life, and 33 breastfed (BF) children (reference group) participating in the COGNIS study. Behavioral problems were evaluated using the Child Behavior Checklist at 18 months and 2.5 years. Different statistical analyses were performed using SPSS. EF children aged 2.5 years presented fewer pathological affective problems than SF children. Besides, SF children were classified more frequently as bordering on internalizing problems than BF children. Rates of externalizing problems were increased in SF infants compared to EF and BF infants. Higher maternal IQ was found to have beneficial effects on internalizing and total problem rate in their offspring at 18 months of life; finally, higher maternal educational level was related with fewer ADHD problems in children at 18 months, as well as internalizing, externalizing, total and anxiety problems in children aged 2.5 years. Our analysis suggests that enriched infant formula fed infants seem to show fewer behavioral problems up to 2.5 years compared to a standard infant formula-fed infants. In addition to type of early feeding, maternal IQ and educational level seem to play a key role on children behavioral development.


Assuntos
Ácidos Graxos Insaturados/administração & dosagem , Glicolipídeos/administração & dosagem , Glicoproteínas/administração & dosagem , Fórmulas Infantis/química , Fenômenos Fisiológicos da Nutrição do Lactente/efeitos dos fármacos , Simbióticos/administração & dosagem , Aleitamento Materno , Comportamento Infantil/efeitos dos fármacos , Desenvolvimento Infantil/efeitos dos fármacos , Pré-Escolar , Método Duplo-Cego , Feminino , Alimentos Fortificados , Humanos , Lactente , Recém-Nascido , Gotículas Lipídicas , Masculino , Transtornos do Neurodesenvolvimento/etiologia , Transtornos do Neurodesenvolvimento/prevenção & controle , Estudos Prospectivos
16.
J Cardiovasc Electrophysiol ; 31(1): 70-79, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31702855

RESUMO

INTRODUCTION: Cardiac implantable electronic device (CIED) infections are associated with a high mortality. Our aim was to identify key predictors of survival in patients with CIED infections as to be able to detect high-risk patients and possibly affect modifiable factors. METHODS AND RESULTS: In this observational study, we collected data from 277 patients with CIED infections treated in our department between 2001 and 2017; predictors of survival were evaluated. The median time since the last CIED procedure was 0.83 years (interquartile range [IQR]: 0.25-3.01), median time since initial CIED implant was 4.79 years (IQR: 0.90-11.0 years). Survival at 30 days was 94.9% (95% confidence interval [CI]: 92.3-97.5) and survival at 1 year was 80.9% (CI: 76.4-85.7). Age (odds ratio [OR]: 1.05, CI: 1.01-1.09; P = .009), end stage renal disease (ESRD) with dialysis (OR: 5.14, CI: 1.87-14.11; P = .001), positive blood cultures (OR: 2.19, CI: 1.08-4.45; P = .030), and thrombocytopenia (OR: 2.3, CI, 1.03-5.15; P = .042) were identified as predictors of death within 1 year of treatment of CIED infection. CONCLUSION: Patients with CIED infection with prior ESRD with dialysis or preoperative thrombocytopenia are at an increased risk of 1-year mortality. We suggest that these patients be evaluated critically and resources be allocated to these patients more liberally. A greater understanding of the role of platelets in immunity may improve treatment of advanced infection in the future.


Assuntos
Desfibriladores Implantáveis/efeitos adversos , Falência Renal Crônica/complicações , Marca-Passo Artificial/efeitos adversos , Infecções Relacionadas à Prótese/etiologia , Trombocitopenia/complicações , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Falência Renal Crônica/diagnóstico , Falência Renal Crônica/mortalidade , Falência Renal Crônica/terapia , Masculino , Pessoa de Meia-Idade , Infecções Relacionadas à Prótese/diagnóstico , Infecções Relacionadas à Prótese/mortalidade , Infecções Relacionadas à Prótese/terapia , Diálise Renal , Medição de Risco , Fatores de Risco , Trombocitopenia/diagnóstico , Trombocitopenia/mortalidade , Fatores de Tempo , Resultado do Tratamento
17.
Nutrients ; 11(10)2019 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-31615134

RESUMO

Postnatal nutrition is essential for growth and neurodevelopment. We analyzed the influence of a new enriched-infant formula with bioactive compounds on growth, neurodevelopment, and visual function (VF) in healthy infants during their first 18 months of life. A total of 170 infants were randomized in the COGNIS randomized clinical trial (RCT) to receive a standard infant formula (SF = 85) or a new experimental infant formula supplemented with functional nutrients (EF = 85). As a control, 50 breastfed infants (BF) were enrolled. Growth patterns were evaluated up to 18 months of life; neurodevelopment was assessed by general movements at 2, 3, and 4 months; VF was measured by cortical visual evoked potentials at 3 and 12 months. No differences in growth and neurodevelopment were found between groups. Regarding VF, SF and EF infants presented prolonged latencies and lower amplitudes in the P100 wave than BF infants. In the EF group, a higher percentage of infants presented response at 7½'of arc at 12 months compared to 3 months of age; a similar proportion of BF and EF infants presented responses at 7½'of arc at 12 months of age. Early nutritional intervention with bioactive compounds could narrow the gap in growth and neurodevelopment between breastfed and formula-fed infants.


Assuntos
Desenvolvimento Infantil/efeitos dos fármacos , Potenciais Evocados Visuais/efeitos dos fármacos , Fórmulas Infantis/análise , Compostos Fitoquímicos/administração & dosagem , Adulto , Aleitamento Materno , Humanos , Lactente , Fenômenos Fisiológicos da Nutrição do Lactente , Pais
18.
Ann Pediatr Cardiol ; 12(3): 206-211, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31516276

RESUMO

BACKGROUND: The pfm Nit-Occlud® patent ductus arteriosus (PDA) device is well established for interventional closure of PDA. However, there are still limited data concerning its efficacy and follow-up in larger patient groups. AIMS: This study aimed to evaluate the safety and efficacy of the Nit-Occlud® PDA device, implanted both through transpulmonary and transaortic approach, in a large cohort. METHODS: From July 2008 to December 2015, 268 consecutive patients were admitted for transcatheter closure of a PDA and were treated with the Nit-Occlud® coil. Clinical, echocardiographic, and angiographic data were evaluated. RESULTS: The median age was 5.2 years (range, 5 months to 62 years), and the median weight was 19.3 kg (range: 5.5-97 kg). Ten (3.7%) patients had weight <10 kg. The most common ductus types treated were Krichenko Type E and A (44.0% and 33.2%, respectively). Twelve (4.5%) patients were treated for residual shunting after surgical PDA closure. The median diameter at the narrowest point was 1.5 mm (range: 0.4-4 mm), the median size of the ampulla was 5 mm (range: 1-15 mm), and the median length was 9 mm (range: 2-25 mm). Device implantation could be successfully achieved in all cases. Closure rates documented immediately after the procedure, at 3-10 days, 1 month, and 6 months after intervention were 62%, 95.1%, 97.8%, and 98.5%, respectively. With the exception of one minor thromboembolic event, there were no procedure-related complications. CONCLUSION: Closure of PDA with various anatomic variations and sizes can be performed effectively and safely using the Nit-Occlud® coil.

19.
J Cardiovasc Electrophysiol ; 30(8): 1371-1372, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31115942

RESUMO

It is unknown how many pacemaker and implantable cardioverter defibrillator (ICD) leads perforate during lead placement. Symptoms of a perforated lead include shortness of breath and chest pain. Signs of perforation can include a high pacing threshold, reduced lead sensing, and a high lead impedance. We present the case of a patient where perforation of the single coil right ventricular lead was not evident in imaging but incidentally detected during operative aortic valve replacement. The lead perforation rate during device implantation is around 1%-ICD leads have a higher perforation rate.


Assuntos
Insuficiência da Valva Aórtica/cirurgia , Bradicardia/terapia , Cardiomiopatia Dilatada/terapia , Desfibriladores Implantáveis/efeitos adversos , Cardioversão Elétrica/efeitos adversos , Cardioversão Elétrica/instrumentação , Traumatismos Cardíacos/etiologia , Implante de Prótese de Valva Cardíaca , Ventrículos do Coração/lesões , Achados Incidentais , Insuficiência da Valva Aórtica/diagnóstico por imagem , Insuficiência da Valva Aórtica/fisiopatologia , Bradicardia/diagnóstico , Bradicardia/fisiopatologia , Cardiomiopatia Dilatada/diagnóstico , Cardiomiopatia Dilatada/fisiopatologia , Remoção de Dispositivo , Traumatismos Cardíacos/diagnóstico , Traumatismos Cardíacos/cirurgia , Ventrículos do Coração/cirurgia , Humanos , Resultado do Tratamento
20.
Biomaterials ; 212: 87-97, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31108275

RESUMO

BACKGROUND: Lack of autologous graft material restricts the ability to treat patients requiring coronary artery bypass surgery (CABG). An off the shelf tissue engineered small diameter vascular graft is the holy grail of cardiovascular surgery. METHODS: Allograft saphenous veins were harvested from organ donors, cryopreserved, deendothelialized and then seeded with autologous endothelial cells prior to implantation during coronary artery bypass surgery. All patients treated were followed-up until death and angiographic results were collected. Grafts were explanted during autopsy and immunohistochemistry was performed. RESULTS: Twelve patients received 15 engineered grafts. Mean patient survival was 9.1 ±â€¯1.8 years. Six month graft patency was 80 (95% CI: 59-100) and 9 month graft patency was 50 (95% CI: 27-93) - graft patency detected up to 32 months after surgery. Immunohistochemistry in grafts explanted showed a presence of CD31 and CD68 positive cells in the luminal region of the vessel walls and layers of Collagen Type I in the abluminal vessel walls. CONCLUSIONS: Our small diameter tissue engineered vascular graft shows openness up to 32 months after implantation. Immunohistochemistry suggests that monocyte activation may lead to vessel remodeling with thickening of the vessel wall. Research should concentrate on a manipulation of remodeling processes.


Assuntos
Aloenxertos/fisiologia , Prótese Vascular , Ponte de Artéria Coronária , Endotélio/fisiologia , Idoso , Prótese Vascular/efeitos adversos , Morte Celular , Determinação de Ponto Final , Feminino , Seguimentos , Oclusão de Enxerto Vascular/etiologia , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/patologia , Complicações Pós-Operatórias/etiologia , Fatores de Tempo
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