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An amendment to this paper has been published and can be accessed via a link at the top of the paper.
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Astronomers have discovered thousands of planets outside the Solar System1, most of which orbit stars that will eventually evolve into red giants and then into white dwarfs. During the red giant phase, any close-orbiting planets will be engulfed by the star2, but more distant planets can survive this phase and remain in orbit around the white dwarf3,4. Some white dwarfs show evidence for rocky material floating in their atmospheres5, in warm debris disks6-9 or orbiting very closely10-12, which has been interpreted as the debris of rocky planets that were scattered inwards and tidally disrupted13. Recently, the discovery of a gaseous debris disk with a composition similar to that of ice giant planets14 demonstrated that massive planets might also find their way into tight orbits around white dwarfs, but it is unclear whether these planets can survive the journey. So far, no intact planets have been detected in close orbits around white dwarfs. Here we report the observation of a giant planet candidate transiting the white dwarf WD 1856+534 (TIC 267574918) every 1.4 days. We observed and modelled the periodic dimming of the white dwarf caused by the planet candidate passing in front of the star in its orbit. The planet candidate is roughly the same size as Jupiter and is no more than 14 times as massive (with 95 per cent confidence). Other cases of white dwarfs with close brown dwarf or stellar companions are explained as the consequence of common-envelope evolution, wherein the original orbit is enveloped during the red giant phase and shrinks owing to friction. In this case, however, the long orbital period (compared with other white dwarfs with close brown dwarf or stellar companions) and low mass of the planet candidate make common-envelope evolution less likely. Instead, our findings for the WD 1856+534 system indicate that giant planets can be scattered into tight orbits without being tidally disrupted, motivating the search for smaller transiting planets around white dwarfs.
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AU Microscopii (AU Mic) is the second closest pre-main-sequence star, at a distance of 9.79 parsecs and with an age of 22 million years1. AU Mic possesses a relatively rare2 and spatially resolved3 edge-on debris disk extending from about 35 to 210 astronomical units from the star4, and with clumps exhibiting non-Keplerian motion5-7. Detection of newly formed planets around such a star is challenged by the presence of spots, plage, flares and other manifestations of magnetic 'activity' on the star8,9. Here we report observations of a planet transiting AU Mic. The transiting planet, AU Mic b, has an orbital period of 8.46 days, an orbital distance of 0.07 astronomical units, a radius of 0.4 Jupiter radii, and a mass of less than 0.18 Jupiter masses at 3σ confidence. Our observations of a planet co-existing with a debris disk offer the opportunity to test the predictions of current models of planet formation and evolution.
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BACKGROUND: Hepatic complications are increasingly recognized after the Fontan operation. The development of hepatocellular carcinoma (HCC) is associated with high mortality when diagnosed, but its incidence and risk factors are poorly understood. We conducted a systematic review and meta-analysis of the cumulative incidence of HCC after Fontan and associated risk factors. METHODS: We searched PubMed, CINAHL, and MEDLINE databases for articles reporting the cumulative incidence of HCC after Fontan operation on March 21, 2023. A single-arm random effects meta-analysis was conducted to assess cumulative incidence at 10, 20, and 30 years after Fontan. Meta-analysis of the difference of the medians was used to assess the influence of risk factors on the development of HCC. RESULTS: Four studies including a total of 1320 patients reported cumulative incidence. The cumulative incidence of HCC at 10, 20, and 30 years after Fontan was 0% (95% CI 0.00-0.01), 2% (0.01-0.06), and 7% (0.03-0.17) respectively. Seven studies including 6,250 patients reported overall incidence of HCC and associated risk factors. At a median 18.4 (IQR 11.9-24.9) years of follow-up, incidence of HCC was 2% (0.01-0.04). Only use of anticoagulation was associated with a lower risk of HCC (RR 0.3, 95% CI 0.1-0.88). DISCUSSION: By 30 years after Fontan, cumulative incidence of HCC is high (7%). Risk of HCC development prior to 10 years post-Fontan is low (0%), though the decision to defer HCC surveillance in this period may require future investigation based on larger studies. Screening with ultrasound every 6 months starting 20 years post-Fontan is reasonable, however, further research regarding timing, cost-effectiveness, additional risk factors associated with HCC risk, and different screening modalities is required.
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OBJECTIVES: The purpose of this study was to define anterior mitral leaflet (AML) length and mitral ring characteristics associated with LVOT obstruction and PVL following MViR. BACKGROUND: Transcatheter Mitral Valve in Ring (MViR) procedural complications including parvalvular leak (PVL) and left ventricular outflow tract (LVOT) obstruction are frequent. METHODS: Clinical records, computer tomographic scans (CTs) and echocardiograms of consecutive MViR patients were retrospectively reviewed for anterior mitral leaflet length, CT-simulated neoLVOT, and aortomitral angle among patients with and without MViR-induced LVOT obstruction. Acute and 1-year outcomes are described. RESULTS: Twenty-two patients underwent MViR. Technical success was achieved in 13/22 (57.1%) patients, limited by paravalvular regurgitation requiring second transcatheter heart valves (THVs) in seven patients. Second valves were needed in 6/11 (54.5%) patients with 3-dimensional rings but 1/11 (9.1%, p = .06) of patients with planar rings. Procedure success at 30 days was achieved in 20/22 (90.9%) patients. There were no procedural, in-hospital, or 30-day deaths. Two patients developed significant LVOT obstruction, one managed with urgent surgery and one with elective alcohol septal ablation. Anterior mitral leaflets were longer among the two patients with LVOT obstruction than the 20 patients who did not develop LVOT obstruction when measured by TEE (30 mm vs. 21 mm, p = .009) or by CT (29 mm vs. 22 mm, p = .026). CONCLUSIONS: AML >25 mm increases the risk of MViR induced LVOT obstruction. PVL is common, particularly in 3-dimensional rings which can be managed with a second THV.
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Implante de Prótese de Valva Cardíaca , Próteses Valvulares Cardíacas , Insuficiência da Valva Mitral , Obstrução do Fluxo Ventricular Externo , Cateterismo Cardíaco/efeitos adversos , Implante de Prótese de Valva Cardíaca/efeitos adversos , Humanos , Valva Mitral/diagnóstico por imagem , Valva Mitral/cirurgia , Insuficiência da Valva Mitral/diagnóstico por imagem , Insuficiência da Valva Mitral/etiologia , Insuficiência da Valva Mitral/cirurgia , Estudos Retrospectivos , Resultado do Tratamento , Obstrução do Fluxo Ventricular Externo/diagnóstico por imagem , Obstrução do Fluxo Ventricular Externo/etiologiaRESUMO
INTRODUCTION: The National Lung Screening Trial (NLST) demonstrated that screening high-risk patients with low-dose computed tomography (CT) of the chest reduces lung cancer mortality compared with screening with chest x-ray. Uninsured and Medicaid patients usually lack access to this hospital-based screening test because of geographic and socioeconomic factors. We hypothesized that a mobile screening unit would improve access and confer the benefits demonstrated by the NLST to this underserved group, which is most at risk of lung cancer deaths. PATIENTS AND METHODS: We created a mobile unit by building a Samsung BodyTom portable 32-slice low-dose CT scanner into a 35-foot coach; it delivers high-quality images for both soft tissue and bone and includes a waiting area and high-speed wireless internet connection for fast image transfer. The unit was extensively tested to show robustness and stability of mobile equipment. This project was designed to screen uninsured and underinsured patients, otherwise with eligibility criteria identical to that of the National Lung Screening Trial, with the only difference being exclusion of patients eligible for Medicare (which provides financial coverage for CT-based lung cancer screening). RESULTS: We screened 550 patients (20% black, 3% Hispanic, 70% rural) with a male-to-female ratio of 1.1:1, median age 61 years (range, 55-64), and found 12 lung cancers at initial screen (2.2%), including 6 at stage I-II (58% of total lung cancers early stage) and 38 Lung-RADS 4 (highly suspicious) lesions that are being followed closely. Incidental findings included nonlung cancers and coronary artery disease. DISCUSSION: In this initial pilot study, using the first mobile low-dose whole body CT screening unit in the U.S., the initial cancer detection rate is comparable to that reported in the NLST, despite excluding patients over the age of 64 years who have Medicare coverage, but with marked improvement of screening rates specifically in underserved sociodemographic, racial, and ethnic groups and with better outcomes than conventionally found in the underserved and at lower cost per case. IMPLICATIONS FOR PRACTICE: This study shows clearly that a mobile low-dose CT scanning unit allows effective lung cancer screening for underserved populations, such as impoverished African Americans, Hispanics, Native Americans, or isolated rural groups, and has a pick-up rate of 1% for early stage disease. If confirmed in a planned randomized trial, this will be policy changing, as these groups usually present with advanced disease; this approach will produce better survival data at lower cost per case.
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Detecção Precoce de Câncer , Neoplasias Pulmonares , Idoso , Feminino , Humanos , Neoplasias Pulmonares/diagnóstico por imagem , Masculino , Programas de Rastreamento , Medicare , Pessoa de Meia-Idade , Projetos Piloto , Tomografia Computadorizada por Raios X , Estados Unidos , Populações VulneráveisRESUMO
BACKGROUND: Current postsurgical atrial fibrillation (AF) ablation guidelines encourage serial rhythm evaluation; however, traditional Holter monitoring may be cumbersome for patients and yield limited data. An implantable loop recorder (LR) may provide increased data on the incidence of postablation arrhythmias. We sought to evaluate the use of a new generation LR implanted during surgical AF ablation. METHODS: A retrospective analysis was performed on adult patients undergoing surgical AF ablation. All patients had subcutaneous placement of a LR. Data were collected on patient demographics, concomitant surgical procedures, complications, loop recorder extraction, and additional arrhythmia interventions. RESULTS: Thirty-one patients underwent surgical AF ablation with intraoperative placement of a LR during the study period. The median age was 71 and the majority had long-standing persistent AF. Mitral and aortic valve pathology was the most common reason for concomitant operations. Four devices were explanted prior to the completion of follow-up due to high AF burdens detected by the LR requiring catheter ablation or pacemaker placement. A 100% correlation between in-clinic rhythm detected by the LR and electrocardiogram was observed. No infectious complications, device malfunctions, or deaths occurred. CONCLUSIONS: LRs placed intraoperatively during surgical ablation of AF are feasible and with nominal, if any, complications. More comprehensive rhythm analysis may aid with determination of operative success and the need for additional intervention or cessation of antiarrhythmic or anticoagulant medications.
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Arritmias Cardíacas/diagnóstico , Fibrilação Atrial/cirurgia , Ablação por Cateter , Eletrocardiografia Ambulatorial/instrumentação , Eletrodos Implantados , Complicações Pós-Operatórias/diagnóstico , Idoso , Idoso de 80 Anos ou mais , Arritmias Cardíacas/epidemiologia , Arritmias Cardíacas/terapia , Eletrocardiografia Ambulatorial/métodos , Estudos de Viabilidade , Feminino , Humanos , Incidência , Período Intraoperatório , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Resultado do TratamentoRESUMO
BACKGROUND: Reducing preventable hospital readmissions after coronary artery bypass graft (CABG) surgery has become a national priority. Predictive models can be used to identify patients at high risk for readmission. However, the majority of the existing models are based on data available at discharge. We sought to develop a model to predict hospital readmission using data available soon after admission for isolated CABG surgery. METHODS: Fifty risk factors were included in a bivariate analysis, 16 of which were significantly associated (P < 0.05) with readmissions and were entered into a multivariate logistic regression and removed stepwise, using backward elimination procedures. The derived model was then validated on 896 prospective isolated CABG cases. RESULTS: Of 2589 isolated CABG patients identified between December 1, 2010, and June 30, 2014, 237(9.15%) were readmitted within 30 days. Five risk factors were predictive of 30-day all-cause readmission: age (odds ratio [OR] = 1.03; 95% confidence interval [CI]: 1.01-1.05; P = 0.004), prior heart failure (OR = 1.55; 95%CI: 1.07-2.24; P = 0.020), total albumin prior to surgery (OR = 0.68; 95%CI: 0.05-0.94; P = 0.021), previous myocardial infarction (OR = 1.44; 95%CI: 1.00-2.08; P = 0.50), and history of diabetes (OR = 1.54; 95%CI: 1.09-2.19; P = 0.015). The area under the curve c-statistic was 0.63 in the derivation sample and 0.65 in the validation sample showing good discrimination. CONCLUSIONS: A 30-day all-cause readmission among isolated CABG patients can be predicted soon after admission with a small number of risk factors.
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Ponte de Artéria Coronária , Admissão do Paciente , Readmissão do Paciente/estatística & dados numéricos , Fatores de Risco , Idoso , Albuminas , Intervalos de Confiança , Diabetes Mellitus , Feminino , Previsões , Insuficiência Cardíaca , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Modelos Estatísticos , Análise Multivariada , Infarto do Miocárdio , Risco , Fatores de TempoRESUMO
Following a Ross procedure, patients may require reintervention for valvular stenosis or insufficiency of either the pulmonary autograft or the pulmonary homograft. Herein is reported a double use of the Medtronic Freestyle stentless bioprosthesis in a patient who previously had undergone a Ross procedure.
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Bioprótese , Implante de Prótese de Valva Cardíaca , Próteses Valvulares Cardíacas , Complicações Pós-Operatórias/cirurgia , Adulto , Humanos , Masculino , Valva Pulmonar/transplanteRESUMO
BACKGROUND: Venous thromboembolism (VTE) is a common cause of serious morbidity and mortality. While chemoprophylaxis decreases VTE, there is the theoretical risk of increased hemorrhagic complications. The purpose of this study was to evaluate the impact of preoperative anticoagulation on VTE and bleeding complications in patients with blunt pelvic fractures requiring operative fixation. METHODS: Patients with blunt pelvic fractures requiring operative fixation over 10.5 years were identified. Patients were stratified by age, severity of shock, operative management, and timing and duration of anticoagulation. Outcomes were evaluated to determine risk factors for bleeding complications and VTE. RESULTS: 310 patients were identified: 212 patients received at least one dose of preoperative anticoagulation and 98 received no preoperative anticoagulation. 68% were male with a mean injury severity score and Glasgow Coma Scale of 26 and 13, respectively. Bleeding complications occurred in 24 patients and 21 patients suffered VTE. Patients with VTE had a greater initial severity of shock (resuscitation transfusions, 4 vs. 2 units, P = .02). Despite longer time to mobilization (4 vs. 3 days, P = .001), patients who received their scheduled preoperative doses within 48 hours of arrival had no significant differences in the number of deep vein thrombosis events (5.2% vs. 5.7%, P = .99), but fewer episodes of pulmonary embolism (PE) (1.5% vs. 6.8%, P = .03) with no difference in bleeding complications (7.5% vs. 8%, P = .87) compared to either patients who had their doses held until after 48 hours of arrival or received no preoperative anticoagulation. DISCUSSION: Preoperative anticoagulation prior to pelvic fixation reduced the risk of PE without increasing bleeding complications. Preoperative anticoagulation is safe and beneficial in this group of patients.
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Anticoagulantes/uso terapêutico , Fraturas Ósseas/cirurgia , Ossos Pélvicos/lesões , Complicações Pós-Operatórias/prevenção & controle , Tromboembolia Venosa/prevenção & controle , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticoagulantes/efeitos adversos , Feminino , Escala de Coma de Glasgow , Heparina/efeitos adversos , Heparina/uso terapêutico , Heparina de Baixo Peso Molecular/efeitos adversos , Heparina de Baixo Peso Molecular/uso terapêutico , Humanos , Escala de Gravidade do Ferimento , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/induzido quimicamente , Complicações Pós-Operatórias/epidemiologia , Hemorragia Pós-Operatória/induzido quimicamente , Hemorragia Pós-Operatória/epidemiologia , Embolia Pulmonar/epidemiologia , Embolia Pulmonar/prevenção & controle , Fatores de Risco , Tromboembolia Venosa/epidemiologia , Adulto JovemRESUMO
BACKGROUND: The HeartMate II (HMII) left ventricular assist device (LVAD) has proven reliable and durable and has become the preferred choice for bridge to transplant therapy (BTT) when compared with the pulsatile HeartMate XVE (XVE). In this study, we compared the post-transplant (PTx) outcomes between XVE and HMII using a large national data registry. METHODS: The Organ Procurement and Transplantation Network (OPTN)/United Network for Organ Sharing (UNOS) Thoracic Registry database was queried for all patients implanted with either an XVE or an HMII as BTT during 2004-2009. Statistical analysis between XVE and HMII were performed using Kaplan-Meier survival analysis and Cox regression analyses. RESULTS: A total of 673 patients were implanted with the XVE and 484 with HMII. When adjusted for age, gender, ethnicity, intra-aortic balloon pump, ventilator, inotropes, dialysis, body mass index, creatinine, bilirubin, transfusion, pulmonary capillary wedge, and pulmonary arterial pressures, the HMII had similar one- and three-yr survival (hazard ratio = 0.95, CI = 0.64, 1.42) and rejection-free survival PTx compared to XVE. The XVE group had more early incidences of allograft rejection (AR) and hospitalization for infection (HI). CONCLUSIONS: Compared to XVE, patients with HMII have similar one- and three-yr survival after heart transplantation with less risk of early graft rejection and significant infection. With a strong shift toward use of continuous-flow LVADs, PTx outcomes are expected to continue to improve.
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Rejeição de Enxerto , Insuficiência Cardíaca/fisiopatologia , Transplante de Coração/mortalidade , Ventrículos do Coração/fisiopatologia , Feminino , Seguimentos , Insuficiência Cardíaca/cirurgia , Ventrículos do Coração/cirurgia , Coração Auxiliar , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Taxa de Sobrevida , Resultado do TratamentoRESUMO
Background: The Core Curriculum Review Course in Cardiovascular and Thoracic Surgery is a 4-day educational program consisting of 77 didactic lectures that provide a comprehensive review of the material required for surgeons preparing for the American Board of Thoracic Surgery competency written examination. The lectures are supplemented with a written syllabus and interactive audience participation system. We sought to determine whether participation in this course could improve participants' performance on a cardiothoracic subject-based test. Methods: Sixty-five participants attended the 2018 course. Before beginning the course lectures, a multiple-choice pretest consisting of 77 questions was administered via mobile application to gauge the participants' baseline knowledge. A second multiple-choice posttest was made available beginning 7 weeks after the course, also by mobile application. Results: Twenty-nine participants completed both the pretest and the posttest. The median pretest score was 47% (36 of 77 correct answers). The median posttest score was 61% (47 of 77 correct answers), representing an increase of 14%. The Wilcoxon signed-rank test indicated a significant difference between the pretest and posttest scores (z = -4.36; P = .00). Overall, 25 participants (86%) improved their posttest score. Conclusions: The core curriculum review course was successful in improving participants' performance on the course tests, indicating that the participants' fund of knowledge was likely increased by attendance at the program. Additional strategies should be considered to address particular areas of study both for individual participants and for residents currently in training.
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Mild traumatic brain injury (TBI) involves widespread axonal injury and activation of microglia, which initiates secondary processes that worsen the TBI outcome. The upregulation of cannabinoid type-2 receptors (CB2) when microglia become activated allows CB2-binding drugs to selectively target microglia. CB2 inverse agonists modulate activated microglia by shifting them away from the harmful pro-inflammatory M1 state toward the helpful reparative M2 state and thus can stem secondary injury cascades. We previously found that treatment with the CB2 inverse agonist SMM-189 after mild TBI in mice produced by focal cranial blast rescues visual deficits and the optic nerve axon loss that would otherwise result. We have further shown that raloxifene, which is Food and Drug Administration (FDA)-approved as an estrogen receptor modulator to treat osteoporosis, but also possesses CB2 inverse agonism, yields similar benefit in this TBI model through its modulation of microglia. As many different traumatic events produce TBI in humans, it is widely acknowledged that diverse animal models must be used in evaluating possible therapies. Here we examine the consequences of TBI created by blunt impact to the mouse head for visual function and associated pathologies and assess raloxifene benefit. We found that mice subjected to impact TBI exhibited decreases in contrast sensitivity and the B-wave of the electroretinogram, increases in light aversion and resting pupil diameter, and optic nerve axon loss, which were rescued by daily injection of raloxifene at 5 or 10 mg/ml for 2 weeks. Raloxifene treatment was associated with reduced M1 activation and/or enhanced M2 activation in retina, optic nerve, and optic tract after impact TBI. Our results suggest that the higher raloxifene dose, in particular, may be therapeutic for the optic nerve by enhancing the phagocytosis of axonal debris that would otherwise promote inflammation, thereby salvaging less damaged axons. Our current work, together with our prior studies, shows that microglial activation drives secondary injury processes after both impact and cranial blast TBI and raloxifene mitigates microglial activation and visual system injury in both cases. The results thus provide a strong basis for phase 2 human clinical trials evaluating raloxifene as a TBI therapy.
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Low vitamin D (serum or plasma 25-hydroxyvitamin D (25(OH)D)) is a global pandemic and associates with a greater prevalence in all-cause and cardiovascular mortality and morbidity. Open-heart surgery is a form of acute stress that decreases circulating 25(OH)D concentrations and exacerbates the preponderance of low vitamin D in a patient population already characterized by low levels. Although supplemental vitamin D increases 25(OH)D, it is unknown if supplemental vitamin D can overcome the decreases in circulating 25(OH)D induced by open-heart surgery. We sought to identify if supplemental vitamin D protects against the acute decrease in plasma 25(OH)D propagated by open-heart surgery during perioperative care. Participants undergoing open-heart surgery were randomly assigned (double-blind) to one of two groups: (a) vitamin D (n = 75; cholecalciferol, 50,000 IU/dose) or (b) placebo (n = 75). Participants received supplements on three separate occasions: orally the evening before surgery and either orally or per nasogastric tube on postoperative days 1 and 2. Plasma 25(OH)D concentrations were measured at baseline (the day before surgery and before the first supplement bolus), after surgery on postoperative days 1, 2, 3, and 4, at hospital discharge (5-8 days after surgery), and at an elective outpatient follow-up visit at 6 months. Supplemental vitamin D abolished the acute decrease in 25(OH)D induced by open-heart surgery during postoperative care. Moreover, plasma 25(OH)D gradually increased from baseline to day 3 and remained significantly increased thereafter but plateaued to discharge with supplemental vitamin D. We conclude that perioperative vitamin D supplementation protects against the immediate decrease in plasma 25(OH)D induced by open-heart surgery. ClinicalTrials.gov Identifier: NCT02460211.
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Procedimentos Cirúrgicos Cardíacos/efeitos adversos , Colecalciferol/administração & dosagem , Suplementos Nutricionais , Assistência Perioperatória , Deficiência de Vitamina D/prevenção & controle , Vitamina D/análogos & derivados , Idoso , Biomarcadores/sangue , Colecalciferol/efeitos adversos , Suplementos Nutricionais/efeitos adversos , Método Duplo-Cego , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Assistência Perioperatória/efeitos adversos , Fatores de Tempo , Resultado do Tratamento , Utah , Vitamina D/sangue , Deficiência de Vitamina D/sangue , Deficiência de Vitamina D/diagnóstico , Deficiência de Vitamina D/etiologiaRESUMO
BACKGROUND: As no standardized curriculum exists for training cardiothoracic surgery residents in surgical ablation for atrial fibrillation there is potential for variation in operative technique, patient selection, and overall application. Thus we sought to assess the exposure of current residents in order to identify areas for improvement in their education. METHODS: A survey was emailed to residents inquiring about their training experience in surgical ablation for atrial fibrillation. Residents were asked about case volume, procedural variety, and guideline-based clinical scenarios where they felt ablation would be appropriate. Residents were also queried about their abilities to perform various lesion sets and overall satisfaction with training. RESULTS: The respondents performed a median of five cases during training with pulmonary vein isolation the most common lesion set. Seventy seven percent of residents are unable to independently perform a bi-atrial (Cox-Maze IV) lesion set. Residents are neutral regarding their satisfaction with training in surgical ablation for atrial fibrillation. CONCLUSIONS: The findings of low case volume, incomplete lesion set use, and lack of training satisfaction suggests residents are being insufficiently exposed to surgical ablation of atrial fibrillation. These findings should inform educators on the importance of a more thorough experience during training given the increasing prevalence of atrial fibrillation and the need for appropriate and durable surgical intervention.
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Visual deficits after traumatic brain injury (TBI) are common, but interventions that limit the post-trauma impairments have not been identified. We have found that treatment with the cannabinoid type-2 receptor (CB2) inverse agonist SMM-189 for 2â¯weeks after closed-head blast TBI greatly attenuates the visual deficits and retinal pathology this otherwise produces in mice, by modulating the deleterious role of microglia in the injury process after trauma. SMM-189, however, has not yet been approved for human use. Raloxifene is an FDA-approved estrogen receptor drug that is used to treat osteoporosis, but it was recently found to also show noteworthy CB2 inverse agonism. In the current studies, we found that a high pressure air blast in the absence of raloxifene treatment yields deficits in visual acuity and contrast sensitivity, reductions in the A-wave and B-wave of the scotopic electroretinogram (ERG), light aversion, and increased pupil constriction to light. Raloxifene delivered daily for two weeks after blast at 5-10â¯mg/kg mitigates or eliminates these abnormalities (with the higher dose generally more effective). This functional rescue with raloxifene is accompanied by a biasing of microglia from the harmful M1 to the helpful M2 state, and reductions in retinal, optic nerve, and oculomotor nucleus pathology. We also found that raloxifene treatment is still effective even when delayed until 48â¯h after TBI, and that raloxifene benefit appears attributable to its CB2 inverse agonism rather than its estrogenic actions. Our studies show raloxifene is effective in treating visual injury after brain and/or eye trauma, and they provide basis for phase-2 efficacy testing in human clinical trials.
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Concussão Encefálica/complicações , Fármacos Neuroprotetores/farmacologia , Cloridrato de Raloxifeno/farmacologia , Receptor CB2 de Canabinoide/efeitos dos fármacos , Transtornos da Visão/etiologia , Animais , Encéfalo/efeitos dos fármacos , Encéfalo/patologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Microglia/efeitos dos fármacos , Microglia/patologia , Nervo Óptico/efeitos dos fármacos , Nervo Óptico/patologia , Receptor CB2 de Canabinoide/agonistas , Retina/patologia , Transtornos da Visão/patologiaRESUMO
OBJECTIVES: The purpose of this study was to evaluate the safety and efficacy of valve-in-valve (ViV) transcatheter aortic valve replacement (TAVR) for stentless bioprosthetic aortic valves (SBAVs) and to identify predictors of adverse events. BACKGROUND: ViV TAVR in SBAVs is associated with unique technical challenges and risks. METHODS: Clinical records and computer tomographic scans were retrospectively reviewed for procedural complications, predictors of coronary obstruction, mortality, and echocardiographic results. RESULTS: Among 66 SBAV patients undergoing ViV TAVR, mortality was 2 of 66 patients (3.0%) at 30 days and 5 of 52 patients (9.6%) at 1 year. At 1 year, left ventricular end-systolic dimension was decreased versus baseline (median [interquartile range (IQR)]: 3.0 [2.6 to 3.6] cm vs. 3.7 [3.2 to 4.4] cm; p < 0.001). Coronary occlusion in 6 of 66 procedures (9.1%) resulted in myocardial infarction in 2 of 66 procedures (3.0%). Predictors of coronary occlusion included subcoronary implant technique compared with full root replacement (6 of 31, 19.4% vs. 0 of 28, 0%; p = 0.01), short simulated radial valve-to-coronary distance (median [IQR]: 3.4 [0.0 to 4.6] mm vs. 4.6 [3.2 to 6.2] mm; p = 0.016), and low coronary height (7.8 [5.8 to 10.0] mm vs. 11.6 [8.7 to 13.9] mm; p = 0.003). Coronary arteries originated <10 mm above the valve leaflets in 34 of 97 unobstructed coronary arteries (35.1%). CONCLUSIONS: TAVR in SBAVs is frequently associated with high-risk coronary anatomy but can be performed with a low risk of death and myocardial infarction, resulting in favorable ventricular remodeling. A subcoronary surgical approach is associated with an increased risk of coronary obstruction.
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Insuficiência da Valva Aórtica/cirurgia , Estenose da Valva Aórtica/cirurgia , Valva Aórtica/cirurgia , Bioprótese , Implante de Prótese de Valva Cardíaca/instrumentação , Próteses Valvulares Cardíacas , Falha de Prótese , Substituição da Valva Aórtica Transcateter/instrumentação , Idoso , Valva Aórtica/diagnóstico por imagem , Valva Aórtica/fisiopatologia , Insuficiência da Valva Aórtica/diagnóstico por imagem , Insuficiência da Valva Aórtica/mortalidade , Insuficiência da Valva Aórtica/fisiopatologia , Estenose da Valva Aórtica/diagnóstico por imagem , Estenose da Valva Aórtica/mortalidade , Estenose da Valva Aórtica/fisiopatologia , Oclusão Coronária/etiologia , Bases de Dados Factuais , Feminino , Implante de Prótese de Valva Cardíaca/efeitos adversos , Implante de Prótese de Valva Cardíaca/mortalidade , Humanos , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/etiologia , Desenho de Prótese , Recuperação de Função Fisiológica , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Fatores de Tempo , Substituição da Valva Aórtica Transcateter/efeitos adversos , Substituição da Valva Aórtica Transcateter/mortalidade , Resultado do Tratamento , Estados UnidosRESUMO
We report the case of a 43-year-old woman with severe coronary artery disease, coarctation of the aorta and dextrocardia. Concomitant repair was achieved by coronary artery bypass grafting and ascending-descending bypass of the proximal descending thoracic aorta.