Perioperative Cannabinoids Significantly Reduce Postoperative Opioid Requirements in Patients Undergoing Coronary Artery Bypass Graft Surgery.

Background Opioids, commonly used to control pain associated with surgery, are known to prolong the duration of mechanical ventilation and length of hospital stay. A wide range of adjunctive strategies are currently utilized to reduce postoperative pain, such as local and regional nerve blocks, nerve cryoablation, and adjunctive medications. We hypothesized that dronabinol (a synthetic cannabinoid) in conjunction with standard opioid pain management will reduce opioid requirements to manage postoperative pain. Methods Sixty-eight patients who underwent isolated first-time coronary artery bypass graft surgery were randomized to either the control group, who received only standard opioid-based analgesia, or the dronabinol group, who received dronabinol (a synthetic cannabinoid) in addition to standard opioid-based analgesia. Dronabinol was given in the preoperative unit, before extubation in the ICU, and after extubation on the first postoperative day. Preoperative, intraoperative, and postoperative parameters were compared under an IRB-approved protocol. The primary endpoints were the postoperative opioid requirement, duration of mechanical ventilation, and ICU length of stay, and the secondary endpoints were the duration of inotropic support needed, left ventricular ejection fraction (LVEF), and the change in LVEF. This study was undertaken at Northwest Medical Center, Tucson, AZ, USA. Results Sixty-eight patients were randomized to either the control group (n = 37) or the dronabinol group (n = 31). Groups were similar in terms of demographic features and comorbidities. The total postoperative opioid requirement was significantly lower in the dronabinol group [39.62 vs 23.68 morphine milligram equivalents (MMEs), p = 0.0037], representing a 40% reduction. Duration of mechanical ventilation (7.03 vs 6.03h, p = 0.5004), ICU length of stay (71.43 vs 63.77h, p = 0.4227), and inotropic support requirement (0.6757 vs 0.6129 days, p = 0.7333) were similar in the control and the dronabinol groups. However, there was a trend towards lower durations in each endpoint in the dronabinol group. Interestingly, a significantly better preoperative to postoperative LVEF change was observed in the dronabinol group (3.51% vs 6.45%, p = 0.0451). Conclusions Our study found a 40% reduction in opioid use and a significantly greater improvement in LVEF in patients treated with adjunctive dronabinol. Mechanical ventilation duration, ICU length of stay, and inotropic support requirement tended to be lower in the dronabinol group, though did not reach statistical significance. The results of this study, although limited by sample size, are very encouraging and validate our ongoing investigation.

Perioperative Left Ventricular Assist Device Use in Patients With Reduced Ejection Fraction Reduces Cardiac Surgery-Associated Acute Kidney Injury.

Background Cardiac surgery may precipitate acute kidney injury (AKI), particularly in patients with poor baseline cardiac function. This is thought to be due to intraoperative renal hypoperfusion, which results in increased morbidity and mortality. This study evaluated the perioperative use of the Impella LD (Abiomed, Danvers, MA) left ventricular assist device (LVAD) in the prevention of postoperative AKI in patients with reduced left ventricular ejection fraction (LVEF) undergoing cardiac surgery. Methods A retrospective analysis was performed at Northwest Medical Center, Tucson, AZ, USA, on patients undergoing valve surgery, coronary artery bypass grafting (CABG), or both by a single surgeon. Those with preoperative LVEF ≤35% and preoperative serum creatinine ≥1 mg/dL were included and segregated based on intraoperative LVAD implantation. Postoperative renal function was assessed using serum creatinine levels and KDIGO (Kidney Disease Improving Global Outcomes) criteria to define AKI. Results Twenty-three patients were enrolled. There were no significant differences in age, demographics, baseline characteristics, or comorbidities between the treatment (n = 12) and the control group (n = 11). In the treatment group, 8% developed AKI by POD#7, while 64% of controls did. The treatment group had a significantly lower mean creatinine change from POD#0-7 (0.07 vs. 0.59, p = 0.02). However, there was no significant difference between groups in the mean creatinine change from baseline to discharge (0.46 vs. 0.42, p = 0.47). Conclusions Our study suggests that intraoperative Impella implantation may reduce the incidence of early postoperative AKI. LVAD implantation is an approach to increase and ensure adequate end-organ (renal) perfusion and can improve postoperative recovery without dialysis requirements. Additional studies are required to understand its protective effects during the perioperative period fully.

Revolutionizing Atrial Fibrillation Treatment: The Robotic Convergent Plus Procedure.

Atrial fibrillation (AF) is widely accepted to be the most common sustained arrhythmia, with an increasing incidence over time. This is thought to be due to the aging population across the world. AF occurs when abnormal electrical foci result in disorganization of atrial depolarization, though the exact pathophysiology leading to these abnormal foci is not well understood. A range of interventions exist for AF - pharmacological therapies (anti-arrhythmic or negative chronotropic medications), cardioversion, or ablations to interrupt the abnormal conduction pathways. Ablation may be via a catheter-based approach, via a surgical approach using the "Maze" procedure (Cox-Maze IV), or more recently, via a hybrid approach. This first involves a surgical epicardial ablation, with catheter-based endocardial ablation following a few weeks later to ensure durable transmural lesion sets via the "Convergent" procedure. We describe the use of the Da Vinci Xi™ robotic platform to improve the procedure, allowing continuous and improved visualization of the anatomy without the need for potentially harmful retraction of the atrial appendage or the back of the left atrium, as well as increased precision with our mapping tools and more complete ablation. Here, we highlight the advantages over a non-robotic (subxiphoid) Convergent procedure, while outlining the key operative steps in undertaking the "Robotic Convergent Plus" procedure using the Da Vinci Xi™ robotic surgical system.

Epicardial placement of human placental membrane protects from heart injury in a swine model of myocardial infarction.

Cardiac ischemic reperfusion injury (IRI) is paradoxically instigated by reestablishing blood-flow to ischemic myocardium typically from a myocardial infarction (MI). Although revascularization following MI remains the standard of care, effective strategies remain limited to prevent or attenuate IRI. We hypothesized that epicardial placement of human placental amnion/chorion (HPAC) grafts will protect against IRI. Using a clinically relevant model of IRI, swine were subjected to 45 min percutaneous ischemia followed with (MI + HPAC, n = 3) or without (MI only, n = 3) HPAC. Cardiac function was assessed by echocardiography, and regional punch biopsies were collected 14 days post-operatively. A deep phenotyping approach was implemented by using histological interrogation and incorporating global proteomics and transcriptomics in nonischemic, ischemic, and border zone biopsies. Our results established HPAC limited the extent of cardiac injury by 50% (11.0 ± 2.0% vs. 22.0 ± 3.0%, p = 0.039) and preserved ejection fraction in HPAC-treated swine (46.8 ± 2.7% vs. 35.8 ± 4.5%, p = 0.014). We present comprehensive transcriptome and proteome profiles of infarct (IZ), border (BZ), and remote (RZ) zone punch biopsies from swine myocardium during the proliferative cardiac repair phase 14 days post-MI. Both HPAC-treated and untreated tissues showed regional dynamic responses, whereas only HPAC-treated IZ revealed active immune and extracellular matrix remodeling. Decreased endoplasmic reticulum (ER)-dependent protein secretion and increased antiapoptotic and anti-inflammatory responses were measured in HPAC-treated biopsies. We provide quantitative evidence HPAC reduced cardiac injury from MI in a preclinical swine model, establishing a potential new therapeutic strategy for IRI. Minimizing the impact of MI remains a central clinical challenge. We present a new strategy to attenuate post-MI cardiac injury using HPAC in a swine model of IRI. Placement of HPAC membrane on the heart following MI minimizes ischemic damage, preserves cardiac function, and promotes anti-inflammatory signaling pathways.

Leveling Up: A Review of Machine Learning Models in the Cardiac ICU.

Machine learning has emerged as a significant tool to augment the medical decision-making process. Studies have steadily accrued detailing algorithms and models designed using machine learning to predict and anticipate pathologic states. The cardiac intensive care unit is an area where anticipation is crucial in the division between life and death. In this paper, we aim to review important studies describing the utility of machine learning algorithms to describe the future of artificial intelligence in the cardiac intensive care unit, especially in regards to the prediction of successful ventilatory weaning, acute respiratory distress syndrome, arrhythmia, and acute kidney injury.

Human Placental Allograft Membranes: Promising Role in Cardiac Surgery and Repair.

Despite the immense investment in research devoted to cardiovascular diseases, mechanisms of progression and potential treatments, it remains one of the leading causes of death in the world. Cellular based strategies have been explored for decades, having mixed results, while more recently inflammation and its role in healing, regeneration and disease progression has taken center stage. Placental membranes are immune privileged tissues whose native function is acting as a protective barrier during fetal development, a state which fosters regeneration and healing. Their unique properties stem from a complex composition of extracellular matrix, growth factors and cytokines involved in cellular growth, survival, and inflammation modulation. Placental allograft membranes have been used successfully in complex wound applications but their potential in cardiac wounds has only begun to be explored. Although limited, pre-clinical studies demonstrated benefits when using placental membranes compared to other standard of care options for pericardial repair or infarct wound covering, facilitating cardiomyogenesis of stem cell populations in vitro and supporting functional performance in vivo. Early clinical evidence also suggested use of placental allograft membranes as a cardiac wound covering with the potential to mitigate the predominantly inflammatory environment such as pericarditis and prevention of new onset post-operative atrial fibrillation. Together, these studies demonstrate the promising translational potential of placental allograft membranes as post-surgical cardiac wound coverings. However, the small number of publications on this topic highlights the need for further studies to better understand how to support the safe and efficient use of placenta allograft membranes in cardiac surgery.

Plasma metagenomic sequencing to detect and quantify bacterial DNA in ICU patients suspected of sepsis: A proof-of-principle study.

BACKGROUND: Timely recognition of sepsis and identification of pathogens can improve outcomes in critical care patients but microbial cultures have low accuracy and long turnaround times. In this proof-of-principle study, we describe metagenomic sequencing and analysis of nonhuman DNA in plasma. We hypothesized that quantitative analysis of bacterial DNA (bDNA) levels in plasma can enable detection and monitoring of pathogens. METHODS: We enrolled 30 patients suspected of sepsis in the surgical trauma intensive care unit and collected plasma samples at the time of diagnostic workup for sepsis (baseline), and 7 days and 14 days later. We performed metagenomic sequencing of plasma DNA and used computational classification of sequencing reads to detect and quantify total and pathogen-specific bDNA fraction. To improve assay sensitivity, we developed an enrichment method for bDNA based on size selection for shorter fragment lengths. Differences in bDNA fractions between samples were evaluated using t test and linear mixed-effects model, following log transformation. RESULTS: We analyzed 72 plasma samples from 30 patients. Twenty-seven samples (37.5%) were collected at the time of infection. Median total bDNA fraction was 1.6 times higher in these samples compared with samples with no infection (0.011% and 0.0068%, respectively, p < 0.001). In 17 patients who had active infection at enrollment and at least one follow-up sample collected, total bDNA fractions were higher at baseline compared with the next sample (p < 0.001). Following enrichment, bDNA fractions increased in paired samples by a mean of 16.9-fold. Of 17 samples collected at the time when bacterial pathogens were identified, we detected pathogen-specific DNA in 13 plasma samples (76.5%). CONCLUSION: Bacterial DNA levels in plasma are elevated in critically ill patients with active infection. Pathogen-specific DNA is detectable in plasma, particularly after enrichment using selection for shorter fragments. Serial changes in bDNA levels may be informative of treatment response. LEVEL OF EVIDENCE: Epidemiologic/Prognostic, Level V.

Expert Consensus Paper: Lateral Thoracotomy for Centrifugal Ventricular Assist Device Implant.

BACKGROUND: The increasing prevalence of heart failure has led to the expanded use of left ventricle assist devices (VADs) for end-stage heart failure patients worldwide. Technological improvements witnessed the development of miniaturized VADs and their implantation through less traumatic non-full sternotomy approaches using a lateral thoracotomy (LT). Although adoption of the LT approach is steadily growing, a lack of consensus remains regarding patient selection, details of the surgical technique, and perioperative management. Furthermore, the current literature does not offer prospective randomized studies or evidence-based guidelines for LT-VAD implantation. METHODS: A worldwide group of LT-VAD experts was convened to discuss these key topics openly. After a PubMed search and review with all authors, a consensus was reached and an expert consensus paper on LT-VAD implantation was developed. RESULTS: This document aims to guide clinicians in the selection of patients suitable for LT approaches and preoperative optimization. Details of operative techniques are described, with an overview of hemisternotomy and bilateral thoracotomy approaches. A review of the best surgical practices for placement of the pump, inflow cannula, and outflow graft provides advice on the best surgical strategies to avoid device malpositioning while optimizing VAD function. Experts' opinions on cardiopulmonary bypass, postoperative management, and approaches for pump exchange and explant are presented. This review also emphasizes the critical need for multidisciplinary teams and specific training. CONCLUSIONS: This expert consensus review provides a compact guide to LT for VAD implantation, from patient selection through intraoperative tips and postoperative management.

Impella 5.5 Direct Aortic Implant and Explant Techniques.

The Impella 5.5 with SmartAssist system (Abiomed, Danvers, MA) is approved for the treatment of cardiogenic shock after acute myocardial infarction, cardiac surgery, or in the setting of cardiomyopathy. Designed for full circulatory support and left ventricular unloading the system comprises a catheter-based microaxial pump placed across the aortic valve, pulling blood from the left ventricle and into the ascending aorta. Implantation can be approached through the axillary artery or directly into the aortic root. We present several technical options for implanting, tunneling, and explanting the system using the direct aortic approach and allowing for bedside removal.

Path to precision: prevention of post-operative atrial fibrillation.

Development of post-operative atrial fibrillation (POAF) following open-heart surgery is a significant clinical and economic burden. Despite advancements in medical therapies, the incidence of POAF remains elevated at 25-40%. Early work focused on detecting arrhythmias from electrocardiograms as well as identifying pre-operative risk factors from medical records. However, further progress has been stagnant, and a deeper understanding of pathogenesis and significant influences is warranted. With the advent of more complex machine learning (ML) algorithms and high-throughput sequencing, we have an unprecedented ability to capture and predict POAF in real-time. Integration of multimodal heterogeneous data and application of ML can generate a paradigm shift for diagnosis and treatment. This will require a concerted effort to consolidate and streamline real-time data. Herein, we will review the current literature and emerging opportunities aimed at predictive targets and new insights into the mechanisms underlying long-term sequelae of POAF.

Continuous-Flow Left Ventricular Assist Devices and Valvular Heart Disease: A Comprehensive Review.

Mechanical circulatory support with implantable durable continuous-flow left ventricular assist devices (CF-LVADs) represents an established surgical treatment option for patients with advanced heart failure refractory to guideline-directed medical therapy. CF-LVAD therapy has been demonstrated to offer significant survival, functional, and quality-of-life benefits. However, nearly one-half of patients with advanced heart failure undergoing implantation of a CF-LVAD have important valvular heart disease (VHD) present at the time of device implantation or develop VHD during support that can lead to worsening right or left ventricular dysfunction and result in development of recurrent heart failure, more frequent adverse events, and higher mortality. In this review, we summarize the recent evidence related to the pathophysiology and treatment of VHD in the setting of CF-LAVD support and include a review of the specific valve pathologies of aortic insufficiency (AI), mitral regurgitation (MR), and tricuspid regurgitation (TR). Recent data demonstrate an increasing appreciation and understanding of how VHD may adversely affect the hemodynamic benefits of CF-LVAD support. This is particularly relevant for MR, where increasing evidence now demonstrates that persistent MR after CF-LVAD implantation can contribute to worsening right heart failure and recurrent heart failure symptoms. Standard surgical interventions and novel percutaneous approaches for treatment of VHD in the setting of CF-LVAD support, such as transcatheter aortic valve replacement or transcatheter mitral valve repair, are available, and indications to intervene for VHD in the setting of CF-LVAD support continue to evolve.

Study of the Expression Transition of Cardiac Myosin Using Polarization-Dependent SHG Microscopy.

Detection of the transition between the two myosin isoforms α- and ß-myosin in living cardiomyocytes is essential for understanding cardiac physiology and pathology. In this study, the differences in symmetry of polarization spectra obtained from α- and ß-myosin in various mammalian ventricles and propylthiouracil-treated rats are explored through polarization-dependent second harmonic generation microscopy. Here, we report for the, to our knowledge, first time that α- and ß-myosin, as protein crystals, possess different symmetries: the former has C6 symmetry, and the latter has C3v. A single-sarcomere line scan further demonstrated that the differences in polarization-spectrum symmetry between α- and ß-myosin came from their head regions: the head and neck domains of α- and ß-myosin account for the differences in symmetry. In addition, the dynamic transition of the polarization spectrum from C6 to C3v line profile was observed in a cell culture in which norepinephrine induced an α- to ß-myosin transition.

Preoperative Risk Stratification of Right Ventricular Function Utilizing Cardiac Magnetic Resonance Imaging Compared With Echocardiographic and Hemodynamic Parameters.

Accurate right ventricle functional analysis prior to mechanical circulatory support continues to be valuable for preoperative stratification of patients at risk for developing right ventricular (RV) failure. While cardiac magnetic resonance imaging (CMR) remains the gold standard, CMR is limited by availability and patient-specific contraindications. Further investigation of other imaging modalities would be beneficial as it may serve as a surrogate to identifying RV systolic dysfunction. A single-center, retrospective study including 29 patients with advanced heart failure was performed. All patients underwent ventricular functional analysis with both CMR and echocardiography, and 19 patients underwent right heart catheterization. Predictability with multimodal assessment of RV function was determined using logistic regression methods. Of the 29 participants, 10 had severe RV dysfunction. Tricuspid annular plane of systolic excursion was a modest predictor of RV dysfunction with odd ratio (OR) of 0.07 (0.01-0.72) and c-statistic of 0.79. Invasive hemodynamic measurement of cardiac index by thermodilution method was also predictive of RV dysfunction but failed to reach statistical significance (OR of 0.03, <0.001-1.28) with c-statistic of 0.83. The role of invasive hemodynamic data in predicting RV function compared with CMR should be further explored among patients with advanced heart failure.

Predictors of Oxygenator Exchange in Patients Receiving Extracorporeal Membrane Oxygenation.

Thrombosis within the membrane oxygenator (MO) during extracorporeal membrane oxygenation (ECMO) can lead to sudden oxygenator dysfunction with deleterious effects to the patient. The purpose of this study was to identify predictors of circuit exchange during ECMO. This is a single-center, retrospective study of all patients who received ECMO at our institution from January 2010 to December 2015. Changes in potential markers were compared on Day 3 vs. Day 0 before MO exchange. Of the 150 patients who received ECMO, there were 58 MO exchanges in 35 patients. Mean ECMO duration was 21.1 (±12.7) days. D-dimer (DD) (µg/mL) (mean difference -2.6; 95% confidence interval [CI]: -4.2 to -1.1; p = .001) increased significantly in the 3 days leading up to MO exchange, whereas fibrinogen (mg/dL) (mean difference 90.7; 95% CI: 41.8-139.6; p = .001), platelet (PLT) count (1,000/µL) (mean difference 23.3; 95% CI: 10.2-36.4; p = .001), and heparin dose (units/h) (mean difference 261.7; 95% CI: 46.3-477.1; p = .02) decreased. Increasing DD or decreasing fibrinogen, PLT count, or heparin dose may indicate an impending need for MO exchange in patients receiving ECMO. Early identification of these changes may help prevent sudden MO dysfunction.

Fluid type influences acute hydration and muscle performance recovery in human subjects.

BACKGROUND: Exercise and heat trigger dehydration and an increase in extracellular fluid osmolality, leading to deficits in exercise performance and thermoregulation. Evidence from previous studies supports the potential for deep-ocean mineral water to improve recovery of exercise performance post-exercise. We therefore wished to determine whether acute rehydration and muscle strength recovery was enhanced by deep-ocean mineral water following a dehydrating exercise, compared to a sports drink or mountain spring water. We hypothesized that muscle strength would decrease as a result of dehydrating exercise, and that recovery of muscle strength and hydration would depend on the type of rehydrating fluid. METHODS: Using a counterbalanced, crossover study design, female (n = 8) and male (n = 9) participants performed a dehydrating exercise protocol under heat stress until achieving 3% body mass loss. Participants rehydrated with either deep-ocean mineral water (Deep), mountain spring water (Spring), or a carbohydrate-based sports drink (Sports) at a volume equal to the volume of fluid loss. We measured relative hydration using salivary osmolality (Sosm) and muscle strength using peak torque from a leg extension maneuver. RESULTS: Sosm significantly increased (p < 0.0001) with loss of body mass during the dehydrating exercise protocol. Males took less time (90.0 ± 18.3 min; P < 0.0034) to reach 3% body mass loss when compared to females (127.1 ± 20.0 min). We used a mono-exponential model to fit the return of Sosm to baseline values during the rehydrating phase. Whether fitting stimulated or unstimulated Sosm, male and female participants receiving Deep as the hydrating fluid exhibited the most rapid return to baseline Sosm (p < 0.0001) regardless of the fit parameter. Males compared to females generated more peak torque (p = 0.0005) at baseline (308.3 ± 56.7 Nm vs 172.8 ± 40.8 Nm, respectively) and immediately following 3% body mass loss (276.3 ± 39.5 Nm vs 153.5 ± 35.9 Nm). Participants experienced a loss. We also identified a significant effect of rehydrating fluid and sex on post-rehydration peak torque (p < 0.0117). CONCLUSION: We conclude that deep-ocean mineral water positively affected hydration recovery after dehydrating exercise, and that it may also be beneficial for muscle strength recovery, although this, as well as the influence of sex, needs to be further examined by future research. TRIAL REGISTRATION: clincialtrials.gov PRS, NCT02486224 . Registered 08 June 2015.

Device Thrombogenicity Emulation: An In Silico Predictor of In Vitro and In Vivo Ventricular Assist Device Thrombogenicity.

Ventricular assist devices (VAD), a mainstay of therapy for advanced and end-stage heart failure, remain plagued by device thrombogenicity. Combining advanced in silico and in vitro methods, Device Thrombogenicity Emulation (DTE) is a device design approach for enhancing VAD thromboresistance. Here we tested DTE efficacy in experimental VAD designs. DTE incorporates iterative design modifications with advanced CFD to compute the propensity of large populations of platelets to activate by flow-induced stresses (statistically representing the VAD 'Thrombogenic Footprint'). The DTE approach was applied to a VAD (MINDTE) design with a favorable thromboresistance profile and compared against a design (MAXDTE) that generated an intentionally poor thromboresistance profile. DTE predictions were confirmed by testing physical prototypes in vitro by measuring VAD thrombogenicity using the modified prothrombinase assay. Chronic in vivo studies in VAD implanted calves, revealed MINDTE calf surviving well with low platelet activation, whereas the MAXDTE animal sustained thromboembolic strokes. DTE predictions were confirmed, correlating with in vitro and in vivo thrombogenicity, supporting utility in guiding device development, potentially reducing the need for animal studies.

Anticoagulant Bridge Comparison in Mechanical Circulatory Support Patients.

Maintaining mechanical circulatory support (MCS) device patients in a specified therapeutic range for anticoagulation remains challenging. Subtherapeutic international normalized ratios (INRs) occur frequently while on warfarin therapy. An effective anticoagulant bridge strategy may improve the care of these patients. This retrospective review of MCS patients with subtherapeutic INRs compared an intravenous unfractionated heparin (UFH) strategy with a subcutaneous enoxaparin or fondaparinux strategy. Native thromboelastography (n-TEG) was used to evaluate anticoagulant effect with coagulation index (CI) as the primary outcome measure. Enoxaparin 0.5 mg/kg subcutaneously (SC) every 12 hours or fondaparinux 2.5-5 mg SC daily were compared with an initial UFH rate of 5 units/kg/hr and titrated to stated n-TEG goal range. The anticoagulant groups UFH, enoxaparin, and fondaparinux were found to be statistically similar with regard to frequency in n-TEG goal range, above range (hypercoagulability), or below range (hypocoagulability). Clinical outcomes were similar among groups with three gastrointestinal bleeds in UFH, one in enoxaparin, and one in fondaparinux groups. Device thrombosis occurred in one UFH patient, while UFH and fondaparinux groups had one ischemic cerebrovascular accident event each. These strategies provided comparable n-TEG results and clinical outcomes when compared with intravenous UFH. Low-dose enoxaparin or fondaparinux may provide an alternative anticoagulant bridging option in MCS patients presenting with subtherapeutic INR.

Is There a Role for Cancer-Directed Surgery in Early-Stage Sarcomatoid or Biphasic Mesothelioma?

BACKGROUND: Benefits of surgical resection for early-stage nonepithelioid malignant pleural mesothelioma (MPM) have not been clearly elucidated. This study investigated whether cancer-directed surgery affects overall survival compared with nonsurgical therapies for T1-T2 N0 M0 sarcomatoid or biphasic MPM patients. METHODS: Adult patients with clinical stage I or II MPM were identified in the National Cancer Database from 2004 to 2103. Patients who underwent cancer-directed surgery were matched by propensity score with patients who had received chemotherapy/radiotherapy or no treatments. Overall survival was compared using a Cox proportional hazard regression model. RESULTS: From National Cancer Database queries, 878 patients with clinical stage I or II MPM with sarcomatoid (n = 524) or biphasic (n = 354) histology were identified. Overall median survival was 5.5 months for patients with sarcomatoid mesothelioma. The cancer-directed surgery improved overall survival compared with no operation (median survival, 7.56 months vs 4.21 months, respectively; p < 0.01). In the biphasic group, median overall survival was 12.2 months. Again, the cancer-directed surgery improved survival compared with no operation (15.8 months vs 9.3 months, p < 0.01). For both histologies, the cancer-directed surgery improved overall survival compared with those who underwent chemotherapy or radiotherapy, or both, without resection (p < 0.05). Perioperative mortality was 6.0% at 30 days and 21.4% at 90 days. CONCLUSIONS: The cancer-directed surgery is associated with improved survival in early-stage MPM patients with nonepithelioid histology compared with those who did not undergo resection or chose medical therapy. Given the high perioperative mortality, a careful patient selection and multidisciplinary evaluation is recommended.