Background:Numerous studies have demonstrated that both cardiopulmonary bypass (CPB) and extracorporeal membrane oxygenation (ECMO) are often associated with adverse outcomes or immune dysregulation when platelet counts decline during support. Moreover, the severity of thrombocytopenia generally correlates with a worse clinical prognosis. However, the underlying mechanisms remain incompletely understood. Previous research has attributed this phenomenon to hemodynamic alterations during CPB and ECMO, as well as anticoagulant-induced abnormal platelet activation. Based on our clinical observations, we question the completeness of this explanation and propose an alternative hypothesis: sustained platelet activation during ECMO serves as an initiating factor that contributes to both progressive thrombocytopenia and immune dysfunction throughout the support period.Methods:We investigated platelet activation status, degranulation capacity, and T cell subset dynamics in patients receiving ECMO support. Flow cytometry was used to assess platelet surface markers, reticulated platelet proportions, and T cell subset distributions.Results:We demonstrate that platelets exhibit excessive activation during ECMO, accompanied by a gradual decline in their degranulation capacity. Notably, even with an increased proportion of newly formed platelets, this functional impairment persists. Furthermore, we observed significant alterations in Helper T cell Type 1 (Th1) and CD8+ T cell populations during ECMO support.Conclusions:Our findings suggest that aberrantly activated platelets during ECMO amplify the specific recognition of platelet antigens by CD8+ T cells via modulating the differentiation bias of CD4+ T cells, particularly Th1 cells, ultimately leading to platelet depletion. These results suggest that early interventions targeting abnormal platelet activation may represent a potentially effective therapeutic strategy to mitigate ECMO-associated thrombocytopenia.

Acute lung injury (ALI) is a severe complication following cardiopulmonary bypass (CPB), associated with high mortality and impaired patient prognosis. At present, there is no effective therapeutic strategy for ALI after CPB. Although the gut microbiota has been implicated in ALI, the biological significance of these associations remains largely elusive. A prospective, single-center, case-control design was adopted. A total of 53 post-CPB patients were enrolled, including 21 in the ALI group and 32 in the non-ALI (NALI) group. Postoperative fecal samples were collected for microbiome and metabolomic analyses, which were subsequently correlated with clinical data. Results revealed that β diversity analysis indicated distinct differences in microbial community structure (Anosim: R = 0.14, P = 0.004; Permanova: R2 = 0.058, P = 0.008). ALI patients exhibited a significant increase in the Bacillota, alongside reductions in Bacteroidota and Actinomycetota. At the genus level, Streptococcus and Enterococcus were enriched in the ALI group, while Bacteroides and Akkermansia were diminished. Metabolomics analysis identified 130 differentially expressed metabolites, 109 of which were significantly reduced in the ALI group, primarily involving amino acid metabolic pathways such as phenylalanine, tryptophan, and tyrosine. A random forest model identified genera such as Bacteroides, Corynebacterium, and Lactobacillus as having high predictive value for ALI (AUC > 0.7). Combined microbiota-metabolite analysis revealed significant correlations between specific genera and differentially expressed metabolites, suggesting a potential role for the gut-lung axis in the development of ALI following CPB. Patients with postoperative ALI following CPB exhibit marked gut microbiota structural disruption and metabolic dysfunction, both closely associated with adverse clinical outcomes. Genera such as Bacteroides and their associated metabolites may serve as early predictive biomarkers, offering novel therapeutic targets for the prevention and management of ALI.

Acute lung injury (ALI) and its severe form, acute respiratory distress syndrome (ARDS), represent a clinical syndrome with high mortality, characterized by excessive pulmonary inflammation and oxidative stress. Despite advancements in conventional supportive care, mortality rates for ALI/ARDS remain persistently high (30

Objectives:In this study, we applied a selective sigma-1 receptor agonist, SA4503, to an extracorporeal cardiopulmonary resuscitation rat model and investigated its cerebral protective effects and potential mechanisms. Methods:Eighteen male adult Sprague-Dawley rats were randomly allocated to 3 groups after anesthesia and identical preparation work, with 6 rats per group. The 2 intervention groups underwent asphyxiation-induced cardiac arrest and were rescued with and without SA4503. The SHAM group did not undergo cardiac arrest or rescue but received the same critical care as the intervention groups until the experiments ended. The end point was 1 hour after the return of spontaneous circulation or death. Hemodynamic and blood gas indicators were measured during surgery. Cerebral injury was evaluated histopathologically. Cerebrospinal fluid samples were collected by microdialysis. Rat hippocampal tissues from the intervention groups were used for whole-transcriptome sequencing. Results:Compared with extracorporeal cardiopulmonary resuscitation (ECPR) group, the ECPR + SA4503 group showed alleviated neuronal destruction of the CA1 region, which is illustrated by the pathologic pictures and the statistical result. In addition, the levels of excitatory amino acids of the ECPR + SA4503 group were lower than that of the ECPR group. In total, 74 differentially expressed genes were detected by RNA sequencing, most of which were related to inflammation, apoptosis, and oxidative stress. The phosphoinositide 3-kinase-AKT signaling pathway was selected by Kyoto Encyclopedia of Genes and Genomes pathway analysis, which may contribute to the cerebral protection of ECPR + SA4503, and was verified via western blotting. Finally, a lncRNA-miRNA-mRNA interactive ceRNA network was established to elucidate the mutual regulation among these three different kinds of RNAs. Conclusions:Our findings indicate that the sigma-1 receptor agonist SA4503 mitigates brain injury in an extracorporeal cardiopulmonary resuscitation rat model.

BACKGROUND AND OBJECTIVE:Pulsatile blood flow is considered more potential for delivering hemodynamic energy and enhancing microcirculatory perfusion in patients compared to non-pulsatile flow in ECMO. This study aims to systematically evaluate the effects of different blood flow modes on the hemodynamic environment, thrombosis risk, and oxygen transport within oxygenators. METHODS:QUADROX-i Adult Oxygenator was investigated using CFD to simulate its hemodynamic environment under different blood flow modes, comprising one non-pulsatile condition and nine pulsatile conditions with varying frequencies and amplitudes. The stasis (ART) and hypercoagulability (C[FXIa]) were used to assess the thrombosis risk and oxygen transport (PO2) was also analyzed. The dynamic blood volume (DBV) were calculated to reflect the effective volume within the oxygenator. RESULTS:Under all blood flow modes, the velocity distribution is more uneven in inlet-side and outlet-side transition regions, and the high value is near the inlet and outlet, and becomes lower away from the inlet and outlet. In gas exchange region, the velocity is low and evenly distributed. The region with the highest ART and C[FXIa] are located at the north corner region close to the outlet. The highest PO2 evenly appears in the region near the outlet. Under pulsatile conditions, As the flow rate increases, the distribution of velocity, ART and C[FXIa] becomes more uneven, and vice verse. Compared to non-pulsatile condition, the period-averaged ART, C[FXIa] and PO2 become higher, while the DBV decreases under pulsatile conditions. Amplitude has a more significant effect on all parameters than frequency. Higher amplitude results in the higher period-averaged ART, C[FXIa] and PO2, alongside a lower DBV. CONCLUSIONS:Uneven flow field mainly occurs in the inlet-side and outlet-side transition region, and the uneven degree increases with the higher flow rate, and vice verse. The highest thrombosis risk locates in the north corner region close to the outlet and the highest oxygen transport occurs in the region close to the outlet. Pulsatile flow can enhance oxygen transport but increase thrombosis risk than non-pulsatile flow. Higher amplitude can increase thrombosis risk but improve oxygen transport in the oxygenator. The frequency variation exhibits minimal influence.

BACKGROUND:The effects of hollow fiber membrane (HFM) configuration on hemodynamic characteristics, oxygen transfer performance, and thrombosis risk in oxygenators are not clear, and the present study was accomplished to investigate these effects. METHODS:Three micro-scale 3D HFM array models were established, with the staggered angle between HFM layers (Φ), the spacing between HFMs (d), and the number of HFM layers (n) as variables. Computational fluid dynamics (CFD) was employed as a predictive tool to quantify wall shear stress (WSS), oxygen partial pressure (PO2), and saturation (SO2), activated coagulation factor XII concentration (C[FXIIa]), blood residence time (BRT), and pressure drop (PD) under various flow rates. RESULTS:It was found that larger Φ resulted in higher outlet-averaged PO2/SO2, more concentrated BRT and C[FXIIa] at lower values, and higher PD. Similar trends in oxygen transfer were observed when d was decreased or n was increased. However, those conditions were associated with more extensive high-BRT and high-C[FXIIa] regions, which were interpreted as indicating higher thrombosis risk. CONCLUSIONS:Based on these predictive results, it is suggested that the inter-layer cross angle should be increased within an acceptable PD range, and that the model porosity should be maintained between 0.4 and 0.6. It is also recommended that the number of layers be reduced for a given volume. Furthermore, it was indicated by the simulations that avoiding extremely large or small flow paths is critical, since larger spacings were predicted to markedly reduce oxygen transfer, while smaller spacings were predicted to increase thrombogenic potential. This study can provide guidance for the design optimization of configurations such as the arrangement of HFMs within the oxygenator.

To explore the factors affecting patient outcomes in pulmonary artery thromboendarterectomy (PTE) under deep hypothermic circulatory arrest (DHCA) and cardiopulmonary bypass (CPB) support and to provide a reference for further improving the effect of PTE. Eighty-five patients with chronic thromboembolic pulmonary hypertension (CTEPH) who underwent PTE under DHCA and CPB support at Beijing Anzhen Hospital from January 2015 to October 2023 were enrolled, including 56 males (65.88

Maternal heart disease is a leading cause of maternal mortality, and the number of pregnant women requiring cardiac surgery has steadily increased despite advancements in diagnostic and therapeutic modalities. Cardiopulmonary bypass (CPB), while providing surgical support, introduces significant perioperative challenges due to the altered maternal physiology and the unique vulnerability of the fetus, with fetal mortality substantially exceeding maternal mortality. Therefore, maternal and fetal protection during CPB necessitates a comprehensive, multidisciplinary strategy encompassing preoperative planning, intraoperative modification, and postoperative management. Key elements include the optimization of surgical timing, precise CPB management with a focus on maintaining uteroplacental perfusion, minimization of inflammatory and ischemic injury to vital organs, safe anesthetic protocols, judicious pharmacological therapy, appropriate use of extracorporeal life support techniques, and continuous fetal heart rate monitoring. The implementation of these systematic maternal-fetal protective strategies is critical to improving both maternal and fetal outcomes in this high-risk population.

Type A aortic dissection (TAAD) is a life-threatening disease with high mortality and poor prognosis, usually treated by surgery. There are many complications in its perioperative period, one of which is oxygenation impairment (OI). As a common complication of TAAD, OI usually occurs throughout the perioperative period of TAAD and requires prolonged mechanical ventilation (MV) and other supportive measures. The purpose of this article is to review the risk factors, mechanisms, and treatments of type A aortic dissection-related oxygenation impairment (TAAD-OI) so as to improve clinicians' knowledge about it. Among risk factors, elevated body mass index (BMI), prolonged extracorporeal circulation (ECC) duration, higher inflammatory cells and stored blood transfusion stand out. A reduced occurrence of TAAD-OI can be achieved by controlling these risk factors such as suppressing inflammatory response by drugs. As for its mechanism, it is currently believed that inflammatory signaling pathways play a major role in this process, including the HMGB1/RAGE signaling pathway, gut-lung axis and macrophage, which have been gradually explored and are expected to provide evidences revealing the specific mechanism of TAAD-OI. Numerous treatments have been investigated for TAAD-OI, such as nitric oxide (NO), continuous pulmonary perfusion/inflation, ulinastatin and sivelestat sodium, immunomodulation intervention and mechanical support. However, these measures are all aimed at postoperative TAAD-OI, and not all of the therapies have shown satisfactory effects. Treatments for preoperative TAAD-OI are not currently available because it is difficult to correct OI without correcting the dissection. Therefore, the best solution for preoperative TAAD-OI is to operate as soon as possible. At present, there is no specific method for clinical application, and it relies more on the experience of clinicians or learns from treatments of other diseases related to oxygenation disorders. More efforts should be made to understand its pathogenesis to better improve its treatments in the future.

Dexmedetomidine is considered to have neuroprotective effects and may reduce postoperative delirium in both cardiac and major non-cardiac surgeries. Compared with non-cardiac surgery, the delirium incidence is extremely high after cardiac surgery, which could be caused by neuroinflammation induced by surgical stress and CPB. Thus, it is essential to explore the potential benefits of dexmedetomidine on the incidence of delirium in cardiac surgery under CPB. Randomized controlled trials studying the effect of perioperative dexmedetomidine on the delirium incidence in adult patients undergoing cardiac surgery with CPB were considered to be eligible. Data collection was conducted by two reviewers independently. The pre-specified outcome of interest is delirium incidence. RoB 2 was used to perform risk of bias assessment by two reviewers independently. The random effects model and Mantel-Haenszel statistical method were selected to pool effect sizes for each study. PubMed, Embase, Cochrane Library, and Web of Science were systematically searched from inception to June 28, 2023. Sixteen studies including 3381 participants were included in our systematic review and meta-analysis. Perioperative dexmedetomidine reduced the incidence of postoperative delirium in patients undergoing cardiac surgery with CPB compared with the other sedatives, placebo, or normal saline (RR 0.57; 95

AbstractAcute lung injury (ALI)/acute respiratory distress syndrome (ARDS) is a severe respiratory condition associated with elevated morbidity and mortality. Understanding their complex pathophysiological mechanisms is crucial for developing new preventive and therapeutic strategies. Recent studies highlight the significant role of inflammation involved in ALI/ARDS, particularly the hyperactivation of the NOD‐like receptor thermal protein domain‐associated protein 3 (NLRP3) inflammasome in macrophages. This activation drives pulmonary inflammation by releasing inflammatory signalling molecules and is linked to metabolic reprogramming, marked by increased glycolysis and reduced oxidative phosphorylation. However, the relationship between NLRP3 inflammasome activation and macrophage glycolytic reprogramming in ALI/ARDS, as well as the molecular mechanisms regulating these processes, remain elusive. This review provides a detailed description of the interactions and potential mechanisms linking NLRP3 inflammasome activation with macrophage glycolytic reprogramming, proposing that glycolytic reprogramming may represent a promising therapeutic target for mitigating inflammatory responses in ALI/ARDS.Key points NLRP3 inflammasome activation is pivotal in mediating the excessive inflammatory response in ALI/ARDS. Glycolytic reprogramming regulates NLRP3 inflammasome activation. Therapeutic potential of targeting glycolytic reprogramming to inhibit NLRP3 inflammasome activation in ALI/ARDS.

Objective: To explore the safety and myocardial protection efficacy of del Nido cardioplegia in adult cardiac and major vascular surgery with long aortic cross-clamp (ACC) time. Methods: A total of 2 536 patients who underwent adult cardiac and major vascular surgery with ACC time>90 min at Beijing Anzhen Hospital from March 2018 to March 2023 were collected. The patients were divided into two groups according to the type of cardioplegia solution: the del Nido cardioplegia solution group (DC group) and the cold blood cardioplegia solution group (BC group). Preoperative baseline data of the patients (age, gender, comorbidities, ejection fraction, etc) were adjusted using propensity score matching (PSM). Cardiopulmonary bypass (CPB) time, ACC time, total amount of cardioplegia solution, in-hospital mortality rate, length of intensive care unit (ICU) stay, mechanical ventilation time, postoperative complications, left ventricular ejection fraction, and troponin levels were compared between the two groups. Results: After PSM, a total of 306 patients were included, including 223 males and 83 females, with a mean age of (52.0±12.3) years. There were 153 cases in the DC group and 153 cases in the BC group. Compared with the DC group, the cross-clamp time was longer [109(100, 150) min vs 102(91, 133) min, P<0.001], the rate of return to spontaneous rhythm was lower [51.6% (79/153) vs 86.9%(133/153), P<0.001], and intraoperative peak glucose was higher [12.6 (6.5, 15.9) mmol/L vs 10.1 (8.5, 12.4) mmol/L, P=0.005] in the BC group. In addition, perioperative mortality [4.6% (7/153) vs 3.3% (5/153), P=0.132], stroke[3.9% (6/153) vs 3.3% (5/153), P=0.759], renal insufficiency [3.3% (5/153) vs 6.5% (10/153), P=0.186], atrial fibrillation [4.6% (7/153) vs 2.6% (4/153), P=0.652] and low cardiac output syndrome [3.9% (6/153) vs 4.6% (7/153), P=0.716] did not differ between the two groups. Compared with BC group, DC group had lower level of high sensitivity troponin (hsTnI) [1.2 (0.8, 1.8) μg/L vs 1.3 (0.9, 2.3) μg/L, P=0.030] and creatine kinase isoenzyme (CK-MB) [31.0 (20.0, 48.9) μg/L vs 37.0 (24.0, 58.9) μg/L, P=0.011] at 24 h postoperatively, and shorter length of ICU stay [35.6 (19.8, 60.5) h vs 42.6 (21.9, 83.6) h, P=0.015] and mechanical ventilation time [20.5 (15.5, 41.0) h vs 31.5 (17.1, 56.0) h, P=0.012]. Subgroup analysis showed that in the 120-180 minute subgroup, patients in the DC group had a shorter cross-clamp time [132 (124, 135) min vs 136 (124, 138) min, P<0.001], while levels of hsTnI [1.6 (1.1, 2.0) μg/L vs 1.4 (1.0, 2.6) μg/L, P=0.030] and CK-MB [38.8 (23.5, 55.5) μg/L vs 37.0 (24.5, 62.3) μg/L, P=0.011] were higher than those in the BC group. Conclusions: In adult cardiac and major vascular surgery with ACC times>90 min, comparable myocardial protection is observed with the use of DC compared with BC. Additional advantages in glycemic control, return to spontaneous rhythm, and improved surgical procedures make DN an attractive alternative for myocardial protection in adult cardiac surgery.

Acute respiratory distress syndrome (ARDS) is an acute inflammatory lung injury characterized by diffuse alveolar damage. The period prevalence of ARDS was 10.4% of ICU admissions in 50 countries. Although great progress has been made in supportive care, the hospital mortality rate of severe ARDS is still up to 46.1%. Moreover, up to now, there is no effective pharmacotherapy for ARDS and most clinical trials focusing on consistently effective drugs have met disappointing results. Mesenchymal stem cells (MSCs) and their derived extracellular vesicles (EVs) have spawned intense interest of a wide range of researchers and clinicians due to their robust anti-inflammatory, anti-apoptotic and tissue regeneration properties. A growing body of evidence from preclinical studies confirmed the promising therapeutic potential of MSCs and their EVs in the treatment of ARDS. Based on the inspiring experimental results, clinical trials have been designed to evaluate safety and efficacy of MSCs and their EVs in ARDS patients. Moreover, trials exploring their optimal time window and regimen of drug administration are ongoing. Therefore, this review aims to present an overview of the characteristics of mesenchymal stem cells and their derived EVs, therapeutic mechanisms for ARDS and research progress that has been made over the past 5 years.

目的:分析美国心血管造影与介入学会(society for cardiovascular angiography and interventions,SCAI)休克分级与静脉-动脉体外膜氧合(venoarterial extracorporeal membrane oxygenation,VA ECMO)支持难治性心源性休克(refractory cardiogenic shock,RCS)患者临床结局的相关性.方法:回顾性分析2017年1月1日至2021年12月31日期间,北京安贞医院VA ECMO支持的RCS患者,根据心源性休克工作组(cardiogenic shock working group,CSWG)共识制定的SCAI休克分级方法对患者进行分组,分别就患者的基本信息、ECMO前基线条件和临床结局比较组间差异.研究的主要终点为出院死亡率,次要终点为ECMO撤除率和30d死亡率.结果:395例患者被纳入研究,中位年龄62(54,67)岁,男性占71.9％.在VA ECMO辅助前,处在SCIA休克分级B级的患者有49例(12.4％),C级78例(19.7％),D级65例(16.5％),E级203例(51.4％).SCAI休克分级是患者住院期间死亡的危险因素,死亡率随分级的升高逐级递增,以SCAI B级为参考,C级:OR=1.509,95％CI:0.703～3.238;D级:OR=2.752,95％CI:1.233～6.142;E 级:OR=3.271,95％CI:1.653～6.474,P＜0.001;ECMO 前心功能NYHAⅢ级以上也是患者死亡的危险因素(OR=2.538,95％CI:1.564～4.119,P＜0.001);相反,罹患心肌炎则是此类患者住院生存的保护性因素(OR=0.133,95％CI:1.564～4.119,P=0.012).SCAI E级患者的ECMO撤除率和住院死亡率均高于B、C级患者,差异有统计学意义(P＜0.001).随着SCAI休克分级的升高,连续肾替代治疗(continuous renal replacement treatment,CRRT)的使用率增加,差异有统计学意义(P＜0.001).处在C级患者的ECMO支持时间、机械通气时间和住院时间最长,其次是D级,ICU时间从C级到E级逐渐减少(P＜0.00l).结论:SCAI休克分级是VAECMO支持心源性休克患者住院死亡的危险因素.

Aorta angiography in IVC-FA. The catheter for contrast medium injection was placed into the descending aorta near the return cannula in the femoral artery. The blood from the return cannula could reach the diaphragm level, but could not supply the upper body. IVC-FA: drainage cannula is placed within the inferior vena cava through the femoral vein and return cannula is in the femoral artery.

OBJECTIVE:Platelet activation by stimulatory factors leads to an increase in intracellular calcium concentration ([Ca2+]i), which is essential for almost all platelet functions. Modulation of Ca2+ influx and [Ca2+]i in platelets has been emerging as a possible strategy for preventing and treating platelet-dependent thrombosis. Voltage-gated potassium 1.3 channels (Kv1.3) are highly expressed in platelets and able to regulate agonist-evoked [Ca2+]i increase. However, the role of Kv1.3 channels in regulating platelet functions and thrombosis has not yet been elucidated. In addition, it is difficult to obtain a specific blocker for this channel, since Kv1.3 shares identical drug-binding sites with other K+ channels. Here, we investigate whether specific blockade of Kv1.3 channels by monoclonal antibodies affects platelet functions and thrombosis. Approach and Results: In this study, we produced the anti-Kv1.3 monoclonal antibody 6E12#15, which could specifically recognize both human and mouse Kv1.3 proteins and sufficiently block Kv1.3 channel currents. We found Kv1.3 blockade by 6E12#15 inhibited platelet aggregation, adhesion, and activation upon agonist stimulation. In vivo treatment with 6E12#15 alleviated thrombus formation in a mesenteric arteriole thrombosis mouse model and protected mice from collagen/epinephrine-induced pulmonary thromboembolism. Furthermore, we observed Kv1.3 regulated platelet functions by modulating Ca2+ influx and [Ca2+]i elevation, and that this is mediated in part by P2X1. Interestingly, Kv1.3-/- mice showed impaired platelet aggregation while displayed no abnormalities in in vivo thrombus formation. This phenomenon was related to more megakaryocytes and platelets produced in Kv1.3-/- mice compared with wild-type mice.CONCLUSIONS:We showed specific inhibition of Kv1.3 by the novel monoclonal antibody 6E12#15 suppressed platelet functions and platelet-dependent thrombosis through modulating platelet [Ca2+]i elevation. These results indicate that Kv1.3 could act as a promising therapeutic target for antiplatelet therapies.

Objectives: The benefit of preoperative intra-aortic balloon pump implantation in high-risk cardiac surgery patients is still debated. The role of preoperative intra-aortic balloon pump insertion in acute myocardial infarction patients without cardiogenic shock undergoing off-pump coronary artery bypass grafting remains unknown. This study aimed to determine the efficacy and safety of the preoperative intra-aortic balloon pump insertion in those patients undergoing off-pump coronary artery bypass grafting. Methods: A total of 421 consecutive acute myocardial infarction patients without cardiogenic shock who underwent isolated off-pump coronary artery bypass grafting were enrolled in this retrospective observational propensity score–matched analysis study. Patients who received intra-aortic balloon pump before off-pump coronary artery bypass grafting (the intra-aortic balloon pump group, n = 157) were compared with those who had not (control group, n = 264). The 30-day postoperative survival, postoperative complications, and postoperative hospital length of stay were compared between the two groups. Results: A total of 99 pairs of patients were matched. The preoperative intra-aortic balloon pump did not show a 30-day postoperative survival benefit compared with the control group (hazard ratio, 0.9; 95% confidence interval, 0.2-4.2; p = 0.92). Patients with preoperative intra-aortic balloon pump were more likely to have shorter postoperative lengths of stay (8 (6-11) days vs. 10 (6-15) days, p = 0.02) and decreased total days in the hospital (median days: 18.2 vs. 21.8, p = 0.02) compared to patients without balloon pumps. Conclusion: Preoperative intra-aortic balloon pump insertion in acute myocardial infarction patients without cardiogenic shock undergoing off-pump coronary artery bypass grafting improved convalescence as shown by significantly shorter postoperative lengths of hospital stay.