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FANCA is a component of the Fanconi anemia (FA) core complex that activates DNA interstrand crosslink repair by monoubiquitination of FANCD2. Here, we report that purified FANCA protein catalyzes bidirectional single-strand annealing (SA) and strand exchange (SE) at a level comparable to RAD52, while a disease-causing FANCA mutant, F1263Δ, is defective in both activities. FANCG, which directly interacts with FANCA, dramatically stimulates its SA and SE activities. Alternatively, FANCB, which does not directly interact with FANCA, does not stimulate this activity. Importantly, five other patient-derived FANCA mutants also exhibit deficient SA and SE, suggesting that the biochemical activities of FANCA are relevant to the etiology of FA. A cell-based DNA double-strand break (DSB) repair assay demonstrates that FANCA plays a direct role in the single-strand annealing sub-pathway (SSA) of DSB repair by catalyzing SA, and this role is independent of the canonical FA pathway and RAD52.
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Reparación del ADN por Unión de Extremidades , Reparación de la Incompatibilidad de ADN , ADN/genética , Proteína del Grupo de Complementación A de la Anemia de Fanconi/genética , Proteína del Grupo de Complementación G de la Anemia de Fanconi/genética , Proteínas del Grupo de Complementación de la Anemia de Fanconi/genética , Reparación del ADN por Recombinación , Animales , Baculoviridae/genética , Baculoviridae/metabolismo , Línea Celular Tumoral , Clonación Molecular , ADN/metabolismo , Roturas del ADN de Doble Cadena , Células Epiteliales/citología , Células Epiteliales/metabolismo , Proteína del Grupo de Complementación A de la Anemia de Fanconi/metabolismo , Proteína del Grupo de Complementación G de la Anemia de Fanconi/metabolismo , Proteínas del Grupo de Complementación de la Anemia de Fanconi/metabolismo , Expresión Génica , Vectores Genéticos/química , Vectores Genéticos/metabolismo , Humanos , Mariposas Nocturnas , Osteoblastos/citología , Osteoblastos/metabolismo , Proteína Recombinante y Reparadora de ADN Rad52/genética , Proteína Recombinante y Reparadora de ADN Rad52/metabolismo , Proteínas Recombinantes/genética , Proteínas Recombinantes/metabolismoRESUMEN
Regulation of stem cells requires coordination of the cells that make up the stem cell niche. Here, we describe a mechanism that allows communication between niche cells to coordinate their activity and shape the signaling environment surrounding resident stem cells. Using the Drosophila hematopoietic organ, the lymph gland, we show that cells of the hematopoietic niche, the posterior signaling center (PSC), communicate using gap junctions (GJs) and form a signaling network. This network allows PSC cells to exchange Ca2+ signals repetitively which regulate the hematopoietic niche. Disruption of Ca2+ signaling in the PSC or the GJ-mediated network connecting niche cells causes dysregulation of the PSC and blood progenitor differentiation. Analysis of PSC-derived cell signaling shows that the Hedgehog pathway acts downstream of GJ-mediated Ca2+ signaling to modulate the niche microenvironment. These data show that GJ-mediated communication between hematopoietic niche cells maintains their homeostasis and consequently controls blood progenitor behavior.
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Proteínas de Drosophila , Animales , Proteínas de Drosophila/metabolismo , Células Madre Hematopoyéticas/metabolismo , Señalización del Calcio , Proteínas Hedgehog/metabolismo , Drosophila/metabolismo , Diferenciación Celular , Uniones Comunicantes/metabolismo , Homeostasis , Nicho de Células Madre , Hematopoyesis/fisiologíaRESUMEN
BACKGROUND: Graft patency is the postulated mechanism for the benefits of coronary artery bypass grafting (CABG). However, systematic graft imaging assessment after CABG is rare, and there is a lack of contemporary data on the factors associated with graft failure and on the association between graft failure and clinical events after CABG. METHODS: We pooled individual patient data from randomized clinical trials with systematic CABG graft imaging to assess the incidence of graft failure and its association with clinical risk factors. The primary outcome was the composite of myocardial infarction or repeat revascularization occurring after CABG and before imaging. A 2-stage meta-analytic approach was used to evaluate the association between graft failure and the primary outcome. We also assessed the association between graft failure and myocardial infarction, repeat revascularization, or all-cause death occurring after imaging. RESULTS: Seven trials were included comprising 4413 patients (mean age, 64.4±9.1 years; 777 [17.6%] women; 3636 [82.4%] men) and 13 163 grafts (8740 saphenous vein grafts and 4423 arterial grafts). The median time to imaging was 1.02 years (interquartile range [IQR], 1.00-1.03). Graft failure occurred in 1487 (33.7%) patients and in 2190 (16.6%) grafts. Age (adjusted odds ratio [aOR], 1.08 [per 10-year increment] [95% CI, 1.01-1.15]; P=0.03), female sex (aOR, 1.27 [95% CI, 1.08-1.50]; P=0.004), and smoking (aOR, 1.20 [95% CI, 1.04-1.38]; P=0.01) were independently associated with graft failure, whereas statins were associated with a protective effect (aOR, 0.74 [95% CI, 0.63-0.88]; P<0.001). Graft failure was associated with an increased risk of myocardial infarction or repeat revascularization occurring between CABG and imaging assessment (8.0% in patients with graft failure versus 1.7% in patients without graft failure; aOR, 3.98 [95% CI, 3.54-4.47]; P<0.001). Graft failure was also associated with an increased risk of myocardial infarction or repeat revascularization occurring after imaging (7.8% versus 2.0%; aOR, 2.59 [95% CI, 1.86-3.62]; P<0.001). All-cause death after imaging occurred more frequently in patients with graft failure compared with patients without graft failure (11.0% versus 2.1%; aOR, 2.79 [95% CI, 2.01-3.89]; P<0.001). CONCLUSIONS: In contemporary practice, graft failure remains common among patients undergoing CABG and is strongly associated with adverse cardiac events.
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Esophagectomy for esophageal cancer is associated with high morbidity. It remains unclear whether prehabilitation, a strategy aimed at optimizing patients' physical and mental functioning prior to surgery, improves postoperative outcomes. A systematic review and meta-analysis was conducted to evaluate the effect of prehabilitation on post-operative outcomes after esophagectomy. Data sources included Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE, CINAHL, and PEDro, with information from 1 January 2000 to 5 August 2023. The analysis included randomized controlled trials and observational studies that compared prehabilitation interventions to standard care prior to esophagectomy. A random effects model was used to generate a pooled estimate for pairwise meta-analysis, meta-analysis of proportions, and meta-analysis of means. A total of 1803 patients were included with 584 in randomized controlled trials (RCTs) and 1219 in observational studies. In the randomized evidence, there were no significant differences between prehabilitation and control in the odds of postoperative pneumonia (15.0 vs. 18.9%, odds ratio (OR) 1.06 [95% confidence interval (CI): 0.66;1.72]) or pulmonary complications (14 vs. 25.6%, OR 0.68 [95% CI: 0.32;1.45]). In the observational data, there was a reduction in both postoperative pneumonia (22.5 vs. 32.9%, OR 0.48 [95% CI: 0.28;0.83]) and pulmonary complications (26.1 vs. 52.3%, OR 0.35 [95% CI: 0.17;0.75]) with prehabilitation. Hospital and intensive care unit length of stay (days), operative mortality, and severe complications (Clavien-Dindo ≥ 3) did not differ between groups in both the randomized data and observational data. Prehabilitation demonstrated reductions in postoperative pneumonia and pulmonary complications in observational studies, but not RCTs. The overall certainty of these findings is limited by the low quality of the available evidence.
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Neoplasias Esofágicas , Neumonía , Humanos , Neoplasias Esofágicas/cirugía , Esofagectomía/efectos adversos , Unidades de Cuidados Intensivos , Neumonía/epidemiología , Neumonía/etiología , Neumonía/prevención & control , Ejercicio Preoperatorio , Ensayos Clínicos Controlados Aleatorios como Asunto , Estudios Observacionales como AsuntoRESUMEN
Ischemic heart disease is the leading cause of death in the United States. Depending on the severity of the coronary artery disease, treatment options include percutaneous coronary intervention (PCI) and coronary artery bypass grafting (CABG). Although CABG has been performed since the 1970s, there is still debate onwhich conduit to use after the left internal thoracic artery. Currently, national registries report the left internal thoracic artery and the saphenous vein as the most commonly used conduits in CABG, while other arterial grafts, such as the radial artery, represent a minority, even though the current evidence suggests potential benefits of these arterial conduits. In this review, we aimed to describe the different types of arterial conduits used for CABG and summarize the evidence behind their use.
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INTRODUCTION: Despite being the preferred modality for treatment of colorectal cancer and diverticular disease, minimally invasive surgery (MIS) has been adopted slowly for treatment of inflammatory bowel disease (IBD) due to its technical challenges. The present study aims to assess the disparities in use of MIS for patients with IBD. METHODS: A retrospective analysis of the National Inpatient Sample (NIS) database from October 2015 to December 2019 was conducted. Patients < 65 years of age were stratified by either private insurance or Medicaid. The primary outcome was access to MIS and secondary outcomes were in-hospital mortality, complications, length of stay (LOS), and total admission cost. Univariate and multivariate regression was utilized to determine the association between insurance status and outcomes. RESULTS: The NIS sample population included 7866 patients with private insurance and 1689 with Medicaid. Medicaid patients had lower odds of receiving MIS than private insurance patients (OR 0.85, 95% CI [0.74-0.97], p = 0.017), and experienced more postoperative genitourinary complications (OR 1.36, 95% CI [1.08-1.71], p = 0.009). In addition, LOS was longer by 1.76 days (p < 0.001) and the total cost was higher by $5043 USD (p < 0.001) in the Medicaid group. Independent predictors of receiving MIS were age < 40 years old, female sex, highest income quartile, diagnosis of ulcerative colitis, elective admission, and care at teaching hospitals. CONCLUSIONS: Patients with Medicaid are less likely to receive MIS, have longer lengths of stay, and incur higher costs for the surgical management of their IBD. Further investigations into disparities in inflammatory bowel disease care for Medicaid patients are warranted.
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Enfermedades Inflamatorias del Intestino , Pacientes Internos , Estados Unidos , Humanos , Femenino , Adulto , Estudios Retrospectivos , Enfermedades Inflamatorias del Intestino/cirugía , Procedimientos Quirúrgicos Mínimamente Invasivos , Cobertura del SeguroRESUMEN
Nucleic acid therapeutics represent a major advance toward treating diseases at their root cause. However, nucleic acids are prone to degradation by serum endonucleases, clearance through the immune system, and rapid degradation in complex medium. To overcome these barriers, nucleic acids frequently include chemical modifications to improve stability or decrease immune responses. Lipid nanoparticles (LNPs) have enabled a dramatic reduction in the dose required to achieve a therapeutic effect by protecting these nucleic acids and improving their intracellular delivery. It has been assumed thus far that nonspecific ionic interactions drive LNP formation and chemical modifications to the nucleic acid backbone to confer improved stability do not impact LNP delivery in any way. Here, we demonstrate that these chemical modifications do impact LNP morphology substantially, and phosphorothioate modifications produce stronger interactions with ionizable amino lipids, resulting in enhanced entrapment. This work represents a major first step toward greater understanding of the interaction between the lipid components and nucleic acids within an LNP.
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Nanopartículas , Ácidos Nucleicos , Liposomas , ARN Interferente PequeñoRESUMEN
OBJECTIVES: Redo sternotomy and explantation of left ventricular assist devices (LVAD) for heart transplantation (HT) involve prolonged dissection, potential injury to mediastinal structures and/or bleeding. Our study compared a complete expanded polytetrafluoroethylene (ePTFE) wrap versus minimal or no ePTFE during LVAD implantation, on outcomes of subsequent HT. METHODS: Between July 2005 and July 2018, 84 patients underwent a LVAD implant and later underwent HT. Thirty patients received a complete ePTFE wrap during LVAD implantation (Group 1), and 54 patients received either a sheet of ePTFE placed in the anterior mediastinum or no ePTFE (Group 2). RESULTS: Baseline characteristics were similar between Groups 1 and 2. Surgeons reported subjective improvements in speed, predictability, and safety of dissection with complete ePTFE compared with minimal or no ePTFE. Time from incision to initiation of cardiopulmonary bypass (CPB) were similar between groups (97 ± 38 vs. 89 ± 29 min, p = .3). Injury to mediastinal structures during the dissection was similar between groups (10% vs. 11%, p > .9). While surgeons reported less intraoperative bleeding in Group 1 (43% vs. 61%), this trend did not reach significance (p = .1). In-hospital mortality, intensive care unit length of stay and hospital length of stay were similar between both groups. CONCLUSIONS: In patients undergoing LVAD explant-HT, there was a trend toward reduced surgeon reported intraoperative bleeding with ePTFE placement. Despite qualitatively reported greater ease and speed of mediastinal dissection with ePTFE membrane placement, time to initiation of CPB did not differ, likely because surgeons remained cautious, allowing extra time for unanticipated difficulties.
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Trasplante de Corazón , Corazón Auxiliar , Humanos , Politetrafluoroetileno , Estudios Retrospectivos , Pericardio/cirugíaRESUMEN
BACKGROUND AND AIM: Lipomatous hypertrophy of the interatrial septum (LHIS), a fatty tumor, is usually diagnosed on both echo and CT/MRI imaging. Cases of LHIS located outside of the interatrial septum are extremely rare and rarer still are these cases large enough to cause symptoms. The clinical literature demonstrates a misunderstanding that fatty tumors outside the intra-atrial area represent lipomas. However, pathologic understanding of these fatty tumors is clear and is based on microscopic findings. METHODS: The tumor was removed by diving the base of attachment at the left ventricular apex via a median sternotomy on cardiopulmonary bypass. RESULTS: The patient made an uneventful recovery and remains well at 6 months postoperatively. CONCLUSIONS: On rare occasions, LHIS can arise from outside the interatrial septum. An LHIS can be differentiated from a lipoma by the presence of entrapped cardiac myocytes in LHIS, making it a pathological, rather than an anatomic, diagnosis.
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Tabique Interatrial/patología , Atrios Cardíacos/patología , Neoplasias Cardíacas/diagnóstico , Neoplasias Cardíacas/patología , Tabiques Cardíacos/patología , Lipoma/diagnóstico , Lipoma/patología , Adulto , Procedimientos Quirúrgicos Cardíacos , Puente Cardiopulmonar , Neoplasias Cardíacas/cirugía , Humanos , Hipertrofia , Lipoma/cirugía , Imagen por Resonancia Magnética , Masculino , Esternotomía , Tomografía Computarizada por Rayos X , Resultado del TratamientoRESUMEN
AIMS: Despite recommendations stating that surgical atrial fibrillation (AF) ablation is reasonable for patients with AF undergoing cardiac surgery for other indications, the clinical impact of this procedure remains unclear. We aimed to describe surgeons' practices and perceptions of this procedure. METHODS AND RESULTS: We built a self-administered survey in collaboration with content and methodology experts. We surveyed 268 cardiac surgeons from 80 centres in 18 countries. The response rate was 76% (n = 204/276), 49% from North America, 39% Europe, and 12% other regions. Respondents performed a median 10 [interquartile range (IQR) 4-30] AF ablation procedures/year, with marked variation in proportions of patients with AF considered for ablation (median 25%, IQR 10-61). 94% and 80% of surgeons respectively, thought symptomatic and asymptomatic patients benefit from ablation. Surgeons estimated the added major complication rate of concomitant AF ablation at 16% [median (IQR) 7-25]. Of participating surgeons, 61% believed that evidence supported surgical AF ablation reducing the incidence of thrombo-embolic complications, and 46% modified anticoagulation decision-making based on whether they performed AF ablation. During coronary artery bypass grafting, isolated pulmonary vein isolation was the most commonly performed lesion set (70%), whereas complete left atrial ablation (46%) and biatrial ablation (44%) were favoured with valve surgery. CONCLUSION: In a multinational group of academic surgeons, surgical AF ablation utilization appears variable, and average case volumes are low. Despite no evidence to that effect, the majority believe that ablation reduces AF-related thrombo-embolic risk of patients. Reported practice patterns suggest clinical equipoise; a definitive trial appears feasible based on respondent willingness to participate.
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Técnicas de Ablación/tendencias , Fibrilación Atrial/cirugía , Cardiólogos/tendencias , Pautas de la Práctica en Medicina/tendencias , Cirujanos/tendencias , Técnicas de Ablación/efectos adversos , Fibrilación Atrial/diagnóstico , Fibrilación Atrial/fisiopatología , Actitud del Personal de Salud , Cardiólogos/psicología , Encuestas de Atención de la Salud , Conocimientos, Actitudes y Práctica en Salud , Disparidades en Atención de Salud/tendencias , Humanos , Cirujanos/psicologíaRESUMEN
BACKGROUND: The incidence of severe coronary artery disease (CAD) in patients with end-stage renal disease (ESRD) on dialysis is high. Coronary artery bypass grafting (CABG) is the preferred treatment in those with severe CAD. Bilateral internal thoracic artery (BITA) vs single internal thoracic artery (SITA) grafting has been shown to improve late survival in other high-risk populations. In ESRD, comparative studies are limited by sample size to detect outcome differences. We sought to determine the late survival and early outcomes of BITA compared with SITA in patients with ESRD. METHODS: MEDLINE and EMBASE were searched from inception to 2017 for studies directly comparing BITA to SITA in patients with ESRD undergoing CABG. The primary outcome was late survival; secondary outcomes were in-hospital/30-day mortality, stroke, and deep sternal wound infection (DSWI). Kaplan-Meier curve reconstruction for late mortality was performed. RESULTS: Five studies (three adjusted [n = 197] and two unadjusted observational studies [n = 231]) were included in the analysis. Reported ITA skeletonization ranged from 83% to 100% (median: 100%). There was no difference in in-hospital mortality (risk risk [RR], 0.84; 95% confidence interval [95%CI], 0.36,1.98; P = 0.70), perioperative stroke (RR, 1.97; 95%CI, 0.58,6.66; P = 0.28), and DSWI (RR, 1.56; 95%CI, 0.60,4.07; P = 0.36) between BITA and SITA. All studies reported adjusted late mortality, which was similar between BITA and SITA (incident rate ratio, 0.81; 95%CI, 0.59,1.11) at mean 3.7-year follow-up. CONCLUSIONS: BITA grafting is safe in patients with ESRD although there was no survival benefit at 3.7 years. Additional studies with longer follow-up are required to determine the potential late benefits of BITA grafting in patients with ESRD.
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Puente de Arteria Coronaria/métodos , Enfermedad de la Arteria Coronaria/cirugía , Fallo Renal Crónico/complicaciones , Arterias Mamarias/trasplante , Puente de Arteria Coronaria/mortalidad , Enfermedad de la Arteria Coronaria/etiología , Bases de Datos Bibliográficas , Diálisis , Humanos , Fallo Renal Crónico/terapia , Tasa de Supervivencia , Resultado del TratamientoRESUMEN
Aims: The aim of this review was to assess the effect of concomitant surgical atrial fibrillation (AF) ablation on postoperative freedom from AF and patient-important outcomes. Methods and results: We searched Cochrane CENTRAL, MEDLINE, and EMBASE databases from inception to May 2016 for randomized controlled trials (RCTs) evaluating surgical AF ablation using any lesion set vs. no surgical AF ablation in adults with AF undergoing cardiac surgery. We performed screening, risk-of-bias evaluation, and data collection independently and in duplicate. We evaluated risk of bias with the modified Cochrane tool, quality of evidence using GRADE framework, and pooled data with a random-effects model. Of the 23 included studies, only one was considered at low risk of bias. Surgical AF ablation was associated with more freedom from AF at 12 months [relative risk (RR) = 2.32, 95% confidence interval (CI) 1.92-2.80; P < 0.001, low quality]. However, no significant difference was seen in mortality (RR = 1.07, 95% CI 0.72-1.52; P = 0.41, moderate quality), stroke (RR = 1.19, 95% CI 0.59-2.39; P = 0.63, moderate quality), or pacemaker implantation (RR = 1.28, 95% CI 0.85-1.95; P = 0.24, high quality). Comparing biatrial and left-sided lesion sets showed no difference in mortality (P-interaction = 0.60) or stroke (P-interaction = 0.12). At 12 months, biatrial procedures led to more freedom from AF (RR = 2.80, 95% CI 2.13-3.68; P < 0.0001) when compared with left-sided ablation (RR = 2.00, 95% CI 1.68-2.39; P < 0.0001) (P-interaction = 0.04) Biatrial procedures appear to increase the risk for pacemaker (RR = 2.68, 95% CI 1.41-5.11; P = 0.002) compared with no ablation while left-sided ablation does not (RR = 1.08, 95% CI 0.67-1.74; P = 0.76) (P-interaction = 0.03). Conclusion: Surgical AF ablation during cardiac surgery improves freedom from AF. However, impact on patient-important outcomes including mortality and stroke has not shown statistical significance in current RCT evidence. Biatrial compared with left-sided lesion sets showed no difference in mortality or stroke but were associated with significantly increased freedom from AF and risk for pacemaker requirement.
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Fibrilación Atrial/cirugía , Procedimientos Quirúrgicos Cardíacos/métodos , Ablación por Catéter/métodos , Criocirugía/métodos , Microondas/uso terapéutico , Fibrilación Atrial/complicaciones , Humanos , Mortalidad , Marcapaso Artificial , Implantación de Prótesis/estadística & datos numéricos , Ablación por Radiofrecuencia/métodos , Ensayos Clínicos Controlados Aleatorios como Asunto , Accidente Cerebrovascular/epidemiología , Accidente Cerebrovascular/etiología , Accidente Cerebrovascular/prevención & control , Resultado del TratamientoAsunto(s)
Calcificación Fisiológica/fisiología , Pericarditis Constrictiva/diagnóstico , Anciano , Ecocardiografía/métodos , Humanos , Masculino , Pericarditis Constrictiva/epidemiología , Pericardio/anomalías , Pericardio/diagnóstico por imagen , Pericardio/fisiopatología , Tomografía Computarizada por Rayos X/métodosRESUMEN
A previously healthy woman in late adolescence presented to the emergency department with stroke-like symptoms following a two-month history of bilateral foot pain and oedema, accompanied by a macular rash and progressive lower extremity weakness. On further investigation, she was found to have multiple cerebral emboli and a left atrial myxoma fixed to the interatrial septum. The patient subsequently underwent urgent surgical excision of the myxoma. On follow-up, her cutaneous and neurological symptoms were significantly improved. This case suggests that, in the presence of a vasculitic rash without evident or obvious cause, cardiac myxoma should be included in the differential diagnosis.
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Embolia , Exantema , Neoplasias Cardíacas , Embolia Intracraneal , Mixoma , Enfermedades Cutáneas Vasculares , Femenino , Humanos , Adolescente , Embolia Intracraneal/etiología , Embolia Intracraneal/complicaciones , Atrios Cardíacos , Enfermedades Cutáneas Vasculares/complicaciones , Embolia/complicaciones , Neoplasias Cardíacas/complicaciones , Neoplasias Cardíacas/diagnóstico por imagen , Neoplasias Cardíacas/cirugía , Mixoma/diagnóstico , Mixoma/diagnóstico por imagen , Exantema/complicacionesRESUMEN
Aortic arch pathology is relatively rare but potentially highly fatal and associated with considerable comorbidity. Operative mortality and complication rates have improved over time but remain high. In response, aortic arch surgery is one of the most rapidly evolving areas of cardiac surgery in terms of surgical volume and improved outcomes. Moreover, there has been a surge in novel devices and techniques, many of which have been developed by or codeveloped with vascular surgeons and interventional radiologists. Nevertheless, the extent of arch surgery, the choice of nadir temperature, cannulation, and perfusion strategies, and the use of open, endovascular, or hybrid options vary according to country, centre, and surgeon. In this review article, we provide a technical overview of the surgical, total endovascular, and hybrid repair options for aortic arch pathology through historical developments and contemporary results. We highlight key information for surgeons, cardiologists, and trainees to understand the management of patients with aortic arch pathology. We conclude by discussing training paradigms, the role of aortic teams, and gaps in knowledge, arguing for the need for wire skills for the future "interventional aortic surgeon" and increased research into techniques and novel devices to continue improving outcomes for aortic arch surgery.
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Aneurisma de la Aorta Torácica , Implantación de Prótesis Vascular , Procedimientos Endovasculares , Cirujanos , Humanos , Aorta Torácica/diagnóstico por imagen , Aorta Torácica/cirugía , Implantación de Prótesis Vascular/métodos , Procedimientos Endovasculares/métodos , Comorbilidad , Aneurisma de la Aorta Torácica/cirugía , Resultado del Tratamiento , StentsRESUMEN
Coronary artery bypass grafting has evolved considerably since it was introduced approximately 50 years ago, with continuously improved patient outcomes as a result of this growth. The most up-to-date evidence on topics such as graft patency, grafting strategy, approaches to graft harvesting, minimally invasive coronary artery bypass grafting, and postoperative pharmacotherapy may lead to changes in current accepted practice. In addition, several unanswered questions in the field of coronary artery bypass grafting may benefit from further investigation and, if resolved, might advance the field and change practice. Current or upcoming clinical trials seek to answer these unanswered questions and may generate data that yields improved outcomes and quality of life for all patients after coronary artery bypass grafting. In addition, cutting edge clinical trials designed specifically for women and racial and ethnic minorities who have had poorer outcomes and have traditionally been underrepresented in cardiovascular surgery research, have recently been launched that may change the way that a large portion of the coronary artery bypass grafting population is treated in the future.
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Individual patient data (IPD) meta-analyses build upon traditional (aggregate data) meta-analyses by collecting IPD from the individual studies rather than using aggregated summary data. Although both traditional and IPD meta-analyses produce a summary effect estimate, IPD meta-analyses allow for the analysis of data to be performed as a single dataset. This allows for standardization of exposure, outcomes, and analytic methods across individual studies. IPD meta-analyses also allow the utilization of statistical methods typically used in cohort studies, such as multivariable regression, survival analysis, propensity score matching, uniform subgroup and sensitivity analyses, better management of missing data, and incorporation of unpublished data. However, they are more time-intensive, costly, and subject to participation bias. A separate issue relates to the meta-analytic challenges when the proportional hazards assumption is violated. In these instances, alternative methods of reporting time-to-event estimates, such as restricted mean survival time should be used. This statistical primer summarizes key concepts in both scenarios and provides pertinent examples.
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Análisis de Supervivencia , HumanosRESUMEN
The burden of coronary artery disease (CAD) is large and growing, commonly presenting with comorbidities and older age. Patients may benefit from coronary revascularisation with percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG), yet half of patients with CAD who would benefit from revascularisation fall outside the eligibility criteria of trials to date. As such, the choice of revascularisation procedures varies depending on the CAD anatomy and complexity, surgical risk and comorbidities, the patient's preferences and values, and the treating team's expertise. The recent American guidelines on coronary revascularisation are comprehensive in describing recommendations for PCI, CABG, or conservative management in patients with CAD. However, individual challenging patient presentations cannot be fully captured in guidelines. The aim of this narrative review is to summarise common clinical scenarios that are not sufficiently described by contemporary clinical guidelines and trials in order to inform heart team members and trainees about the nuanced considerations and available evidence to manage such cases. We discuss clinical cases that fall beyond the current guidelines and summarise the relevant evidence evaluating coronary revascularisation for these patients. In addition, we highlight gaps in knowledge based on a lack of research (eg, ineligibility of certain patient populations), underrepresentation in research (eg, underenrollment of female and non-White patients), and the surge in newer minimally invasive and hybrid techniques. We argue that ultimately, evidence-based medicine, patient preference, shared decision making, and effective heart team communications are necessary to best manage complex CAD presentations potentially benefitting from revascularisation with CABG or PCI.
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Enfermedad de la Arteria Coronaria , Intervención Coronaria Percutánea , Humanos , Femenino , Enfermedad de la Arteria Coronaria/cirugía , Puente de Arteria Coronaria/métodos , Resultado del TratamientoRESUMEN
BACKGROUND: There is limited report of outcomes in women undergoing isolated coronary artery bypass grafting (CABG) with left internal thoracic artery and different second conduits (saphenous vein graft [SVG], radial artery [RA], and right internal thoracic artery [RITA]). METHODS: The National Adult Cardiac Surgery Audit database was queried for women undergoing isolated CABG with left internal thoracic artery graft in the United Kingdom from 1996 to 2019. Propensity score-based pairwise comparisons were performed between graft types. The primary outcome was in-hospital mortality. RESULTS: The study included 58,063 women (SVG, n = 48,881 [84.2%]; RA, n = 6136 [10.6%]; RITA, n = 2445 [4.2%]). SVG use was stable over the years; RA and RITA use decreased. In-hospital mortality was similar between the RA and RITA grafts (2.3% vs 2.8%; odds ratio [OR], 0.80; 95% CI, 0.53-1.22; P = .39) and between the RA and SVG (2.3% vs 2.0%; OR, 1.20; 95% CI, 0.93-1.55; P = .17) but higher in the RITA group compared with the SVG (2.7% vs 1.4%; OR, 2.04; 95% CI, 1.27-3.36; P = .004). Women receiving the RITA graft were more likely to have sternal wound infection (SWI) compared with the RA (0.6% vs 0.06%; P = .004) and the SVG (0.6% vs 0.2%; P = .032). SWI was consistently associated with higher risk of in-hospital mortality. CONCLUSIONS: Conduit selection may affect operative outcomes in women undergoing CABG. The RA shows similar mortality and risk of deep SWI as the SVG.