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OBJECTIVES: The association between obesity and graft failure after coronary artery bypass grafting has not been previously investigated. METHODS: We pooled individual patient data from randomized clinical trials with systematic postoperative coronary imaging to evaluate the association between obesity and graft failure at the individual graft and patient levels. Penalized cubic regression splines and mixed-effects multivariable logistic regression models were performed. RESULTS: Six trials comprising 3928 patients and 12 048 grafts were included. The median time to imaging was 1.03 (interquartile range 1.00-1.09) years. By body mass index (BMI) category, 800 (20.4%) patients were normal weight (BMI 18.5-24.9), 1668 (42.5%) were overweight (BMI 25-29.9), 983 (25.0%) were obesity class 1 (BMI 30-34.9), 344 (8.8%) were obesity class 2 (BMI 35-39.9) and 116 (2.9%) were obesity class 3 (BMI 40+). As a continuous variable, BMI was associated with reduced graft failure [adjusted odds ratio (aOR) 0.98 (95% confidence interval (CI) 0.97-0.99)] at the individual graft level. Compared to normal weight patients, graft failure at the individual graft level was reduced in overweight [aOR 0.79 (95% CI 0.64-0.96)], obesity class 1 [aOR 0.81 (95% CI 0.64-1.01)] and obesity class 2 [aOR 0.61 (95% CI 0.45-0.83)] patients, but not different compared to obesity class 3 [aOR 0.94 (95% CI 0.62-1.42)] patients. Findings were similar, but did not reach significance, at the patient level. CONCLUSIONS: In a pooled individual patient data analysis of randomized clinical trials, BMI and obesity appear to be associated with reduced graft failure at 1 year after coronary artery bypass grafting.
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Índice de Masa Corporal , Puente de Arteria Coronaria , Obesidad , Sobrepeso , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Puente de Arteria Coronaria/efectos adversos , Obesidad/complicaciones , Sobrepeso/complicaciones , Sobrepeso/epidemiología , Ensayos Clínicos Controlados Aleatorios como Asunto , Factores de RiesgoRESUMEN
BACKGROUND: Women undergoing coronary artery bypass grafting (CABG) have higher operative mortality than men. OBJECTIVES: The purpose of this study was to evaluate the relationship between intraoperative anemia (nadir intraoperative hematocrit), CABG operative mortality, and sex. METHODS: This was a cohort study of 1,434,225 isolated primary CABG patients (344,357 women) from the Society of Thoracic Surgeons Adult Cardiac Surgery Database (2011-2022). The primary outcome was operative mortality. The attributable risk (AR) (the risk-adjusted strength of the association of female sex with CABG outcomes) for the primary outcome was calculated. Causal mediation analysis derived the total effect of female sex on operative mortality risk and the proportion of that effect mediated by intraoperative anemia. RESULTS: Women had lower median nadir intraoperative hematocrit (22.0% [Q1-Q3: 20.0%-25.0%] vs 27.0% [Q1-Q3: 24.0%-30.0%], standardized mean difference 97.0%) than men. Women had higher operative mortality than men (2.8% vs 1.7%; P < 0.001; adjusted OR: 1.36; 95% CI: 1.30-1.41). The AR of female sex for operative mortality was 1.21 (95% CI: 1.17-1.24). After adjusting for nadir intraoperative hematocrit, AR was reduced by 43% (1.12; 95% CI: 1.09-1.16). Intraoperative anemia mediated 38.5% of the increased mortality risk associated with female sex (95% CI: 32.3%-44.7%). Spline regression showed a stronger association between operative mortality and nadir intraoperative hematocrit at hematocrit values <22.0% (P < 0.001). CONCLUSIONS: The association of female sex with increased CABG operative mortality is mediated to a large extent by intraoperative anemia. Avoiding nadir intraoperative hematocrit values below 22.0% may reduce sex differences in CABG operative mortality.
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Anemia , Procedimientos Quirúrgicos Cardíacos , Adulto , Humanos , Femenino , Masculino , Estudios de Cohortes , Puente de Arteria Coronaria/efectos adversos , Anemia/epidemiología , Hematócrito , Factores de Riesgo , Resultado del Tratamiento , Estudios RetrospectivosRESUMEN
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
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.
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Enfermedad de la Arteria Coronaria , Arterias Mamarias , Adulto , Humanos , Femenino , Resultado del Tratamiento , Estudios Retrospectivos , Puente de Arteria Coronaria , Arterias Mamarias/trasplante , Reino Unido/epidemiología , Arteria Radial/trasplante , Vena Safena/trasplante , Enfermedad de la Arteria Coronaria/cirugíaRESUMEN
The external stenting of saphenous vein grafts (SVGs) during coronary artery bypass grafting (CABG) has been proven to reduce intimal hyperplasia (IH) in animal models, paving the way for human randomized controlled trials (RCTs) to be conducted. Herein, we performed a study-level meta-analysis to assess the impact of the Venous External SupporT (VEST) device, an external stent, on the outcomes of SVGs. A systematic search was conducted to identify all RCTs comparing VEST-stented to non-stented SVGs in patients undergoing CABG. The primary outcome was graft occlusion. The main secondary outcomes were repeat revascularization, SVG IH area, and intimal-medial thickness. Two RCTs totaling 407 patients were included. At a mean follow-up of 1.5 years, there was no difference in graft occlusion between groups (incidence rate ratio: 1.11; 95% confidence interval (CI): 0.80-1.53). The rate of repeat revascularization was also similar (odds ratio: 0.66; 95% CI: 0.27-1.64). The IH area (standardized mean difference (SMD): -0.45; 95% CI: -0.79 to -0.10) and intimal-medial thickness (SMD: -0.50; 95% CI: -0.90 to -0.10) were significantly reduced in the VEST group. Our findings show that significant reductions in the IH area and the intimal-medial thickness in VEST-stented SVGs do not currently translate into a lesser need for repeat revascularization or less graft occlusion events compared to non-stented SVGs at 1.5 years after CABG.
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OBJECTIVE: To review the available literature on the use of coronary artery bypass grafting (CABG) as a treatment option for anomalous origin of coronary artery in adults. METHODS: A systematic literature search was performed in March 2023 (including Ovid MEDLINE, Ovid Embase, and the Cochrane Library databases) to identify studies reporting the use of CABG in adult patients with anomalous origin of coronary artery. RESULTS: A total of 31 studies and 62 patients were included, 32 patients (52%) were women, and the mean age was 45.1±16.1 years. The most common coronary anomaly was the right coronary artery arising from the left coronary sinus in 26 patients (42%), followed by an anomalous left coronary artery from the pulmonary artery in 23 patients (37%). A total of 65 conduits were used in 61 patients, and 1 case report did not report conduit type. Reported grafts included saphenous vein (23 of 65 [35.4%]), left internal thoracic artery (15 of 65 [23.1%]), right internal thoracic artery (23 of 65 [35.4%]), and radial artery (2 of 65 [3.1%]); right gastroepiploic artery and basilic vein were used once (1.5%) each. Ligation of the native coronary artery was performed in 42 (67.7%) patients. Patient follow-up was available in 19 studies with a mean of 31.2 months. Only 1 operative mortality was reported. CONCLUSIONS: Based on the limited available data, CABG can be performed with good early results. Use of arterial conduits and ligation of the native coronary artery may improve long-term graft patency.
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Vasos Coronarios , Arterias Mamarias , Adulto , Femenino , Humanos , Masculino , Persona de Mediana Edad , Angiografía Coronaria , Puente de Arteria Coronaria/métodos , Vasos Coronarios/diagnóstico por imagen , Vasos Coronarios/cirugía , Arterias Mamarias/trasplante , Arteria Radial/trasplante , Vena Safena/trasplante , Resultado del Tratamiento , Grado de Desobstrucción VascularRESUMEN
Saphenous vein grafts (SVGs) are the most frequently used conduits in coronary artery bypass grafting (CABG), but their higher rate of occlusion compared to arterial conduits remains a concern. Previous studies have shown that SVG failure is mainly driven by intimal hyperplasia, an adaptative response to higher pressures of the arterial circulation. The VESTTM device (Vascular Graft Solutions, Tel Aviv, Israel), an external support designed to mitigate intimal hyperplasia in SVGs, has been tested in few clinical trials (RCTs). Herein, we descriptively evaluated the randomized evidence on the VEST device.
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Background: Spinal cord injury (SCI) is a rare but severe complication after open or endovascular repair of descending thoracic aneurysms (DTAs) or thoracoabdominal aortic aneurysms (TAAAs). This meta-analysis aims to provide a comprehensive assessment of SCI rates and factors associated with SCI. Methods: A systematic literature search was performed in September 2022 looking for studies on open and/or endovascular repair of DTA and/or TAAA published after 2018, to update the results of our previously published meta-analysis. The primary outcome was permanent SCI. Secondary outcomes were temporary SCI, 30-day and in-hospital mortality, follow-up mortality, postoperative stroke, and cerebrospinal fluid (CSF) drain-related complications. Data were pooled as proportions using inverse-variance weighting. Results: A total of 239 studies (71 new studies and 168 from our previous meta-analysis) and 61,962 patients were included. The overall pooled rate of permanent SCI was 3.3% [95% confidence interval (CI), 2.9-3.8%]. Open repair was associated with a permanent SCI rate of 4.0% (95% CI, 3.3-4.8%), and endovascular repair was associated with a permanent SCI rate of 2.9% (95% CI, 2.4-3.5%). Permanent SCI was 2.0% (95% CI, 1.2-3.3%) after DTA repair, and 4.7% (95% CI, 3.9-5.6%) after TAAA repair; permanent SCI rate was 3.8% (95% CI, 2.9-5.0%) for Crawford extent I, 13.4% (95% CI, 9.0-19.5%) for extent II, 7.1% (95% CI, 5.7-8.9%) for extent III, 2.3% (95% CI, 1.6-3.5%) for extent IV, and 6.7% (95% CI, 1.7-23.1%) for extent V TAAA aneurysms. The pooled rate of CSF drain related complications was 1.9% (95% CI, 0.8-4.7%) for severe, 0.4% (95% CI, 0.0-4.0%) for moderate, and 1.8% (95% CI, 0.6-5.6%) for minor complications. Conclusions: Permanent SCI occurs after both endovascular and open DTA or TAAA repairs. Open repairs and TAAA repairs have higher risk of SCI compared with endovascular or DTA repairs. In particular, extent II aneurysms present the highest overall risk of SCI.
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Background and Objective: Coronary artery bypass grafting (CABG) is the most commonly performed cardiac surgery globally and in the United States, however, women have worse outcomes than men. We aim to examine the possible drivers of this sex difference in CABG outcomes. Methods: A narrative review using a current search of the most recent literature on this topic. Key Content and Findings: The sex difference in outcomes after CABG has persisted despite advances in the field, with women having well-described worse operative mortality and morbidity than men. Several explanatory mechanisms have been proposed for these differences. These include, but are not limited to, preoperative factors such as the natural history of coronary artery disease in women, older age, and higher prevalence of comorbidities at the time of presentation for CABG surgery. Intraoperative factors have also been proposed to play a role, including the smaller coronary artery size and greater coronary artery reactivity in women, the degree of intraoperative hemodilution anemia, the type of grafting, and the completeness of revascularization. However, no definitive etiology has been identified to date. Conclusions: The sex difference in outcomes after CABG remains present, and despite numerous proposed etiopathologies, the main driver remains unclear. Further research is needed to identify, and address, the root cause of this difference, and greater participation of women in cardiovascular and cardiac surgery trials is crucial.
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BACKGROUND: Postoperative atrial fibrillation (POAF) is the most frequent complication of cardiac surgery. Despite clinical and economic implications, ample variability in POAF assessment method and definition exist across studies. We performed a study-level meta-analysis to evaluate the influence of POAF assessment method and definition on its incidence and association with clinical outcomes. METHODS AND RESULTS: A systematic literature search was conducted to identify studies comparing the outcomes of patients with and without POAF after cardiac surgery that also reported POAF assessment method. The primary outcome was POAF incidence. The secondary outcomes were in-hospital mortality, stroke, intensive care unit length of stay, and postoperative length of stay. Fifty-nine studies totaling 197 774 patients were included. POAF cumulative incidence was 26% (range: 7.3%-53.1%). There were no differences in POAF incidence among assessment methods (27%, [range: 7.3%-53.1%] for continuous telemetry, 27% [range: 7.9%-50%] for telemetry plus daily ECG, and 19% [range: 7.8%-42.4%] for daily ECG only; P>0.05 for all comparisons). No differences in in-hospital mortality, stroke, intensive care unit length of stay, and postoperative length of stay were found between assessment methods. No differences in POAF incidence or any other outcomes were found between POAF definitions. Continuous telemetry and telemetry plus daily ECG were associated with higher POAF incidence compared with daily ECG in studies including only patients undergoing isolated coronary artery bypass grafting. CONCLUSIONS: POAF incidence after cardiac surgery remains high, and detection rates are variable among studies. POAF incidence and its association with adverse outcomes are not influenced by the assessment method and definition used, except in patients undergoing isolated coronary artery bypass grafting.
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Fibrilación Atrial , Procedimientos Quirúrgicos Cardíacos , Accidente Cerebrovascular , Humanos , Fibrilación Atrial/diagnóstico , Fibrilación Atrial/epidemiología , Fibrilación Atrial/etiología , Incidencia , Procedimientos Quirúrgicos Cardíacos/efectos adversos , Puente de Arteria Coronaria/efectos adversos , Accidente Cerebrovascular/diagnóstico , Accidente Cerebrovascular/epidemiología , Accidente Cerebrovascular/complicaciones , Complicaciones Posoperatorias/diagnóstico , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/etiología , Factores de RiesgoRESUMEN
Randomized clinical trials (RCTs) have a key role in progressing biomedical research and guiding clinical decision making, but premature termination remains high (up to 30%), raising concerns regarding funding expenditure and resource allocation. This brief report sought to identify variables associated with RCTs' premature termination and completion.
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Investigación Biomédica , Humanos , Ensayos Clínicos Controlados Aleatorios como AsuntoRESUMEN
Coronary artery bypass grafting is the most commonly performed cardiac surgical procedure. Conduit selection is crucial to achieving early optimal outcomes, with graft patency being likely the main driver to long-term survival. We present a review of current evidence on the patency of arterial and venous bypass conduits and of differences in angiographic outcomes.
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Coronary artery bypass grafting (CABG) is the most frequently performed cardiac surgery worldwide. The reported incidence of graft failure ranges between 10% and 50%, depending upon the type of conduit used. Thrombosis is the predominant mechanism of early graft failure, occurring in both arterial and vein grafts. Significant advances have been made in the field of antithrombotic therapy since the introduction of aspirin, which is regarded as the cornerstone of antithrombotic therapy for prevention of graft thrombosis. Convincing evidence now exists that dual antiplatelet therapy (DAPT), consisting of aspirin and a potent oral P2Y12 inhibitor, effectively reduces the incidence of graft failure. However, this is achieved at the expense of an increase in clinically important bleeding, underscoring the importance of balancing thrombotic risk and bleeding risk when considering antithrombotic therapy after CABG. In contrast, anticoagulant therapy has proved ineffective at reducing the occurrence of graft thrombosis, pointing to platelet aggregation as the key driver of graft thrombosis. We provide a comprehensive review of current practice for prevention of graft thrombosis and discuss potential future concepts for antithrombotic therapy including P2Y12 inhibitor monotherapy and short-term DAPT.
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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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BACKGROUND: Deep sternal wound infections are rare but severe complications after median sternotomy and can be managed with sternal reconstruction. The use of pectoralis major flap (PMF) has traditionally been the first-line approach for flap reconstruction but the advantage in patients' survival when compared to the omental flap (OF) transposition is still not clear. We performed a study-level meta-analysis evaluating the association of the type of flap on postoperative outcomes. METHODS: A systematic search of the literature was performed to identify all studies comparing the postoperative outcomes of PMF versus OF for sternal reconstruction. The primary outcome was postoperative mortality. Secondary outcomes were the occurrence of sepsis, pneumonia, operative time, and length of stay. Binary outcomes were pooled using an inverse variance method and reported as odds ratio (OR) with corresponding 95% confidence interval (CI). Continuous outcomes were pooled using an inverse variance method and reported as standardized mean difference (SMD) with corresponding 95% CI. RESULTS: Four studies with a total of 528 patients were included in the analysis. Overall, 443 patients had PMF reconstruction, and 85 patients had OF reconstruction. Baseline characteristics were similar in both groups. There were no statistically significant differences between PMF patients and OF patients in mortality (OR 0.6 [0.16; 2.17]; p = .09), sepsis (OR 1.1 [0.49; 2.47]; p = .43), pneumonia (OR 0.72 [0.18; 2.8]; p = .11), length of stay (SMD -0.59 [-2.03; 0.85]; p < .01), and operative time (SMD 0.08 [-1.21; 1.57]; p < .01). CONCLUSION: Our analysis found no association between the type of flap and postoperative mortality, the incidence of pneumonia, sepsis, operation time, and length of stay.
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Mediastinitis , Músculos Pectorales , Humanos , Músculos Pectorales/trasplante , Mediastinitis/etiología , Mediastinitis/cirugía , Infección de la Herida Quirúrgica/etiología , Colgajos Quirúrgicos , Esternón/cirugía , Esternotomía/efectos adversos , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
Background: Posterior pericardiotomy (PP) has been shown to reduce the incidence of pericardial effusion and postoperative atrial fibrillation (POAF) after cardiac surgery. However, the procedure and the totality of its effects are poorly known in the cardiac surgery community. We performed a study-level meta-analysis of randomized controlled trials (RCTs) to evaluate the impact of PP in cardiac surgery patients. Methods: A systematic literature search was conducted on three medical databases (Ovid MEDLINE, Ovid Embase, Cochrane Library) to identify RCTs reporting outcomes of patients that received a PP or no intervention after cardiac surgery. The primary outcome was the incidence of POAF. Key secondary outcomes were operative mortality, incidence of pericardial and pleural effusion, cardiac tamponade, length of stay (LOS), pulmonary complications, amount of chest drainage, need for intra-aortic balloon pump, and re-exploration for bleeding. Results: Eighteen RCTs totaling 3,531 patients were included. PP was associated with a significantly lower incidence of POAF (odds ratio [OR] 0.45, 95% confidence interval [CI] 0.32-0.64, P < 0.0001), early (OR 0.18, 95% CI 0.10-0.34, P < 0.0001) and late pericardial effusion (incidence rate ratio 0.13, 95% CI 0.06-0.29, P < 0.0001), and cardiac tamponade (risk difference -0.02, 95% CI -0.04 to -0.01, P = 0.001). PP was associated with a higher incidence of pleural effusion (OR 1.42, 95% CI 1.06-1.90, P = 0.02), but not pulmonary complications (OR 0.82, 95% CI 0.56-1.19; P = 0.38). No differences in other outcomes, including operative mortality, were found. Conclusions: PP is a safe and effective intervention that significantly decreases the incidence of POAF and pericardial effusion following cardiac surgery. Systematic review registration: https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=261485, identifier: CRD42021261485.
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To perform a systematic review of studies prospectively analyzing the impact of regionalization of complex surgical oncology care on patient outcomes. High volume care of complex surgical oncology patients has been repeatedly associated with improved outcomes. Most studies, however, are retrospective and have not prospectively accounted for confounders such as financial ability and social support. Four electronic databases (Ovid MEDLINE®, Ovid EMBASE, Cochrane Library (Wiley), and EBSCHOHost) were searched from inception until August 25, 2018. Two authors independently reviewed 5887 references, with a third independent reviewer acting as arbitrator when needed. Data extracted from 11 articles that met inclusion criteria. Risk of bias assessments conducted using MINORS criteria for the non-randomized, observational studies, and the Cochrane tool for the randomized-controlled trial. Of the 11 studies selected, we found 7 historically-controlled trials, two retrospective cohort studies with prospective data collection, one prospective study, and one randomized-controlled trial. 73% of studies were from Northern Europe, 18% from Ontario, Canada, and 9% from England. Pancreatic surgery accounted for 36% of studies, followed by gynecologic oncology (27%), thoracic surgery (18%), and dermatologic surgery (9%). The studies reported varying outcome parameters, but all showed improvement post-regionalization. Included studies featured poor-to-fair risk of bias. 11 studies indicated improved outcomes following regionalization of surgical oncology, but most exhibit poor methodological rigor. Prospective evidence for the regionalization of surgical oncology is lacking. More research addressing patient access to care and specialist availability is needed to understand the shortcomings of centralization.