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Current dogma dictates that, during adulthood, endothelial cells (ECs) are locked in an immutable stable homeostatic state. By contrast, herein we show that maintenance of EC fate and function are linked and active processes, which depend on the constitutive cooperativity of only two ETS transcription factors (TFs), ERG and Fli1. Although deletion of either ERG or Fli1 manifests subtle vascular dysfunction, their combined genetic deletion in adult ECs results in acute vasculopathy and multi-organ failure, due to loss of EC fate and integrity, hyperinflammation and spontaneous thrombosis, leading to death. ERG and Fli1 co-deficiency causes rapid transcriptional silencing of pan and organotypic vascular core genes, with dysregulation of inflammation and coagulation pathways. Vascular hyperinflammation leads to impaired hematopoiesis with myeloid skewing. Accordingly, enforced ERG and FLI1 expression in adult human mesenchymal stromal cells activates vascular programs and functionality, enabling in vivo engraftment of a perfusable vascular network. Genome-wide association study analysis identified vascular diseases that are associated with FLI1/ERG mutations. Constitutive expression of ERG and Fli1 upholds EC fate, physiological function and resilience in adult vasculature, whereas their functional loss can contribute to systemic human diseases.

OBJECTIVES Among patients with ascending thoracic aortic aneurysms, prosthetic graft replacement yields major benefits but risk for recurrent aortic events persists for which mechanism is poorly understood. This pilot study employed cardiac magnetic resonance to test the impact of proximal prosthetic grafts on downstream aortic flow and vascular biomechanics. METHODS Cardiac magnetic resonance imaging was prospectively performed in patients with thoracic aortic aneurysms undergoing surgical (Dacron) prosthetic graft implantation. Imaging included time resolved (4-dimensional) phase velocity encoded cardiac magnetic resonance for flow quantification and cine-cardiac magnetic resonance for aortic wall distensibility/strain. RESULTS Twenty-nine patients with thoracic aortic aneurysms undergoing proximal aortic graft replacement were studied; cardiac magnetic resonance was performed pre- [12 (4, 21) days] and postoperatively [6.4 (6.2, 7.2) months]. Postoperatively, flow velocity and wall shear stress increased in the arch and descending aorta (P CONCLUSIONS Prosthetic graft replacement of the ascending aorta increases downstream aortic wall shear stress and strain. Postoperative increments in descending aortic wall shear stress correlate with reduced ascending aortic distensibility, suggesting that grafts provide a nidus for high energy flow and adverse distal aortic remodelling.

Valve-sparing root replacement using reimplantation techniques is increasingly applied to bicuspid aortopathy. Long-term durability of cusp repair is unclear. We analyze midterm results using a conservative approach to cusp repair.From 2006 to 2018, 327 patients underwent valve-sparing reimplantation, 66 with bicuspid valves. Leaflets were analyzed after reimplantation. A majority (51/66) required no cusp repair. Fifteen patients had cusp repair limited to closure of unfused raphe or central plication. Patients were followed by echocardiography.Mean age of patients was 44.7 ± 12.3 years. The cusp repair group had a higher incidence of preoperative moderate (10% vs 40%) or severe (4% vs 33.3%) aortic insufficiency (P .001). There was no operative mortality or major complication. Mean follow-up was 51.6 ± 40.8 months. On postoperative echocardiography, incidence of none, trace, or mild aortic insufficiency was 41.3% (19/46), 43.5% (20/46), and 15.2% (7/46) in the no cusp repair group and 40% (6/15), 40% (6/15), and 20% (3/15) in the cusp repair group, respectively (P = .907). Few patients progressed in degree of aortic insufficiency. No patients required reoperation. At 5 years, freedom from any aortic insufficiency was 46.9% versus 15.8% (P = .013), and freedom from greater than trace aortic insufficiency was 59.1% versus 36.9% (P = .002) due to the higher rate of postoperative trace and mild aortic insufficiency with cusp repair. There was no difference in freedom from greater than mild aortic insufficiency (92.1% vs 100%; P = .33).Valve-sparing root replacement is reliably performed with bicuspid aortic valves whether or not cusp reconstruction is necessary. Few patients progress to greater than mild aortic insufficiency. Need for reoperation is rare in midterm follow-up.

During November 2018–April 2019, an 11-station very high frequency (VHF) Lightning Mapping Array (LMA) was deployed to Córdoba Province, Argentina. The purpose of the LMA was validation of the Geostationary Lightning Mapper (GLM), but the deployment was coordinated with two field campaigns. The LMA observed 2.9 million flashes (≥ five sources) during 163 days, and level-1 (VHF locations), level-2 (flashes classified), and level-3 (gridded products) datasets have been made public. The network’s performance allows scientifically useful analysis within 100 km when at least seven stations were active. Careful analysis beyond 100 km is also possible. The LMA dataset includes many examples of intense storms with extremely high flash rates (>1 s−1), electrical discharges in overshooting tops (OTs), as well as anomalously charged thunderstorms with low-altitude lightning. The modal flash altitude was 10 km, but many flashes occurred at very high altitude (15–20 km). There were also anomalous and stratiform flashes near 5–7 km in altitude. Most flashes were small (2 area). Comparisons with GLM on 14 and 20 December 2018 indicated that GLM most successfully detected larger flashes (i.e., more than 100 VHF sources), with detection efficiency (DE) up to 90%. However, GLM DE was reduced for flashes that were smaller or that occurred lower in the cloud (e.g., near 6-km altitude). GLM DE also was reduced during a period of OT electrical discharges. Overall, GLM DE was a strong function of thunderstorm evolution and the dominant characteristics of the lightning it produced.

Objective Cerebral protection for aortic arch surgery has been widely studied, but comparisons of all the available strategies have rarely been performed. We performed direct and indirect comparisons of antegrade cerebral perfusion, retrograde cerebral perfusion, and deep hypothermic circulatory arrest in a network meta-analysis. Methods After a systematic literature search, studies comparing any combination of antegrade cerebral perfusion, retrograde cerebral perfusion, and deep hypothermic circulatory arrest were included, and a frequentist network meta-analysis was performed using the generic inverse variance method. The primary outcomes were postoperative stroke and operative mortality. Secondary outcomes were postoperative transient neurologic deficits, myocardial infarction, respiratory complications, and renal failure. Results A total of 68 studies were included with a total of 26,968 patients. Compared with deep hypothermic circulatory arrest, both antegrade cerebral perfusion and retrograde cerebral perfusion were associated with significantly lower postoperative stroke and operative mortality rates: antegrade cerebral perfusion (odds ratio [OR], 0.62; 95% confidence interval [CI], 0.51-0.75; and OR, 0.63, 95% CI, 0.51-0.76, respectively) and retrograde cerebral perfusion (OR, 0.66; 95% CI, 0.54-0.82; and OR, 0.57; 95% CI, 0.45-0.71, respectively). Antegrade cerebral perfusion and retrograde cerebral perfusion were associated with similar incidence of primary outcomes. No difference among the 3 techniques was found in secondary outcomes. At meta-regression, circulatory arrest duration correlated with the neuroprotective effect of antegrade cerebral perfusion and retrograde cerebral perfusion compared with deep hypothermic circulatory arrest. Unilateral or bilateral antegrade cerebral perfusion and arrest temperature did not influence the results. Conclusions Antegrade cerebral perfusion and retrograde cerebral perfusion are associated with better postoperative outcomes compared with deep hypothermic circulatory arrest, and the relative benefit increases with the duration of the circulatory arrest. No differences between antegrade cerebral perfusion and retrograde cerebral perfusion were found for all the explored outcomes.

Endothelial cells are critical mediators of health and disease. Regenerative medicine techniques that target the endothelium hold vast promise for improving lifespan and quality of life worldwide. Regenerative therapies via induced pluripotent stem cells (IPSCs) have helped demonstrate disease mechanisms, but so far, concerns regarding their function, malignant potential, and expense have limited therapeutic potential. One alternative approach is direct reprogramming of somatic cells, which avoids the pluripotent state and allows for in vivo reprogramming. Transcription factors from endothelial development have yielded essential transcription factors and small molecules that induce endothelial cell fate. Most direct cell reprogramming strategies targeting endothelial cells use ETV2, a pioneer transcription factor to specify endothelial lineage via histone-modifying enzymes. Many different types of starting cells and strategies, including lentiviral transduction, inducing innate immunity, and small molecule signaling have been leveraged for reprogramming. However, so far therapeutic benefit of these strategies remains unproven. Future research will have to solve scalability, safety, and efficacy hurdles before being ready for the clinic. However, researchers have already discovered meaningful insights into disease mechanisms and development through direct reprogramming.

Background The radial artery has been used for coronary artery bypass surgery for more than 25 years. The recent confirmation of the clinical benefits associated with the use of the artery is likely to drive a new interest toward this conduit in the next few years. Methods A group of surgeons with extensive experience in the systematic use of the radial artery summarize here the key technical aspects of the use of the conduit for coronary bypass operations. Results Preoperative evaluation of the ulnar collateral circulation and attention to the characteristics of the target vessel are keys for the successful use of the radial artery. Open or endoscopic harvesting can be used, preferentially with the aid of the harmonic scalpel. The use of vasodilatory and antispastic protocols is probably important but poorly supported by the current evidence. The radial artery can be used for multiple grafting strategies with a variable degree of technical complexity. Conclusions With attention to few technical key points, the radial artery is a versatile conduit that can be easily introduced in the everyday practice of coronary artery bypass surgery.

Studies on the association between care quality, case volume, and outcomes in coronary artery bypass grafting (CABG) have concluded that consistent adherence to quality measures improves mortality rates and outcomes. However, the quality metrics are not well-defined, and their significance to surgeons and healthcare providers remains uncertain. We review the concept of "quality and quality metrics" and discuss their importance in the context of CABG.

Objective Sinus of Valsalva (SOV) aneurysms are rare and data on operative management are limited. They can cause right ventricular outflow tract or pulmonary artery compression, and rupture may be fatal. In this study, we describe our experience with the repair of 13 SOV aneurysms. Methods All patients who underwent SOV aneurysm repair from May 2001 to December 2017 at our single tertiary referral center were reviewed retrospectively. Results Thirteen patients (92% male) with a mean age of 60 years underwent repair of an SOV aneurysm; mean aneurysm diameter was 5.9 ± 0.8 cm and four patients (30.7%) presented with rupture into another cardiac chamber. Operative interventions included six Bentall procedures, five patch repairs (one with aortic valve replacement [AVR]), and two primary aneurysm closures both with concomitant AVR. There were no strokes, myocardial infarctions, re-explorations, or deaths in the postoperative period. After an average of 2.25 years, computed tomographic imaging in five patients demonstrated no aneurysm recurrence. Conclusions Surgery is a safe option for both ruptured and nonruptured SOV aneurysms. A variety of repair strategies may be used. Larger studies are needed.

Background AngioVac is a new device for filtering intravascular thrombi and emboli. Publications on the device are limited and underpowered to objectively estimate its safety and efficacy. We aimed to overcome this by performing a meta-analysis on the results of AngioVac for treating venous thromboses and endocardial vegetations. Methods A systematic literature review was performed to identify all articles reporting cardiac vegetation and/or thrombosis extraction using AngioVac. Endpoints were successful removal, operative mortality, conversion to open surgery, hospital stay, recurrent thromboembolism, and follow-up mortality. Random effect model was used, and pooled event rates (PERs) and incidence rate (IR) were calculated. Results A total of 42 studies with 182 patients (81 vegetation and 101 thrombosis) were included. Overall mean follow-up times were 3.1 and 0.7 years in vegetation and thrombosis patients, respectively. The PERs for successful removal were 74.5 (confidence interval [CI]: 48.2-90.2), 80.5 (CI: 70.0-88.0), and 32.4 (CI: 17.0-52.8) in vegetation, right atrial/caval venous thrombi, and pulmonary emboli (PE) patients, respectively. The PERs for operative mortalities were 14.6 (CI: 7.7-25.8), 14.8 (CI: 8.5-24.5), and 32.3 (CI: 15.1-56.3), respectively. The PERs for conversion to open surgery were 25.0 (CI: 9.3-51.9) and 12.3 (CI: 5.4-25.6) in vegetation and thrombosis patients, respectively. The IR of recurrent thromboembolism was 0.18 per person per year (PPY) (CI: 0.00-14.69) in vegetation and 0.19 PPY (CI: 0.08-0.48) in thrombosis patients. IR of follow-up mortality was 0.37 PPY (CI: 0.11-1.21) in thrombosis patients. Conclusions AngioVac is a viable option for extracting right-sided vegetations and right atrial/caval venous thrombi. Rates of successful extraction and mortality are significantly worse for PE.

Background Minimally invasive mitral valve surgery (MIMVS) is performed with increasing frequency. However, patients undergoing MIMVS might be at increased risk of perioperative stroke, mainly due to retrograde aortic embolization during femoral cardio-pulmonary bypass. Pre-operative computed tomography (CT) screening allows visualization of the aorta and femoro-iliac vessels and individualization of the surgical approach. In this meta-analysis, we aim to determine if systematic pre-operative CT screening is associated with decreased incidence of post-operative stroke and other complications following MIMVS. Methods A comprehensive review was performed in PubMed (inception-May 2018). Eligible studies included those which reported on MIMVS (mini-thoracotomy, port access or robotic approach) with retrograde arterial perfusion. Studies were separated into two subgroups: systematic pre-operative CT screening (CT-group) and no CT screening (Non-CT). Pooled event rates (PER) for operative mortality, post-operative stroke, perioperative myocardial infarction (MI), and new onset renal failure requiring dialysis were estimated and inter-group comparisons were performed. Results Data from 57 studies (13,731 patients) were analyzed (19 CT-group, 38 Non-CT). PER for post-operative stroke was 2.0% with a statistically significant difference between the groups (CT-group: 1.5% versus Non-CT: 2.2%, P = 0.03). PER for new dialysis was 1.9%, significantly lower in the CT-group (0.8% versus 2.3% in the Non-CT group, P = 0.02). PER for operative mortality was 1.4% with a trend towards better outcomes in the CT-group (0.8% versus 1.6% in the Non-CT group, P = 0.05). Conclusions Systematic pre-operative CT screening is associated with lower risk of post-operative stroke and need for dialysis and a trend toward lower operative mortality after MIMVS.

The evidence for volume-outcome relationships across different surgical procedures including aortic and mitral valve surgery is mostly limited to facility level and/or annual assessments ([1][1],[2][2]). Cumulative surgical expertise is important in some surgical procedures ([3][3]) and needs to be

Background Pulmonary artery aneurysms (PAAs) are a rare but potentially lethal cardiovascular pathology. PAAs tend to develop in young patients with no gender discrepancy; they are most often associated with congenital heart disorders but also with systemic infections, vasculitis, pulmonary arterial hypertension, chronic pulmonary embolism, and malignancies. Dissection and rupture carry significant morbidity and mortality, thus patients require careful management, especially those with associated pulmonary hypertension. Given the rarity of this condition, physicians have yet to establish standard treatment guidelines. Most studies published to date are case reports with one or two patients; here, we describe our experience with six cases of large PAAs treated surgically at our institution. Methods We identified and retrospectively analyzed clinical data for patients who underwent surgery for PAAs between 2009 and 2017. Results The average age at surgery was 59.73 years, five patients were females, and 83.3% had baseline hypertension. Systolic murmurs were the most common clinical finding. The average aneurysmal size was 65.0 mm. We repaired the PAA with a woven Dacron graft (22-26 mm) in four patients. We performed concomitant pulmonary valve procedures on five patients: four replacements and one repair. Mean pump and cross-clamp times were 108.5 and 65 minutes. Operative and 30-day mortality was 0%. Average length of stay was 10.5 days. Conclusions Postoperative mortality was 0%; all patients showed improvement of symptoms after surgery. These findings confirm that PAA repair has an acceptable risk profile in select patients.

Purpose Cancer of the heart is rare but lethal. For those few patients with primary or metastatic cardiac malignancy, options for treatment are limited. Heart transplantation as a treatment for cardiac malignancy has been suggested by several small case series but outcomes data are scarce. We present a series of 104 heart transplants performed for any cancer involving the heart from 1982 to 2017 from the International Society of Heart and Lung Transplant (ISHLT) Thoracic Organ Transplant Registry. Methods 104 heart recipients were identified with cancer as the indication for transplant. We performed Kaplan-Meier survival analyses matching the 104 cancer patients with 104 patients receiving heart transplants for hypertrophic cardiomyopathy (HCM) because both cohorts are young with few co-morbidities. Matching was based on age, gender and transplant year. Results Median survival in the cancer cohort was 3.6 years (95% Confidence Interval (CI) = 1.2,7.2) compared to 17.5 (CI 16.6, 19.0) years in the matched HCM group (Table). Mortality was not significantly different at 30 days, but at the end of 5 years, more than half of the cancer patients were dead (Figure). 27 of these deaths were due to cancer. In the Cox-proportional hazards model, transplant for cardiac malignancy correlated with mortality (HR=1.8 (CI=1.1-3.1), p=0.02). Conclusion This study presents the largest retrospective series to date of heart transplantations performed for cancer. These patients had significantly increased mortality due to tumor recurrence. This raises a concern about allocating donor hearts for malignancy.

We thank Dr. de Souza and colleagues for their careful and thorough evaluation of our recent patient-level meta-analysis (1). They have provided an excellent summary of our methods and findings which we will not spend time repeating here. Instead, we will give an adequate reply to their critique. The issues raised in their paper are important and deserve careful consideration. Our response will address the foremost of their concerns which is the exclusion of the Orebro study by Dreifeldt et al . from our analysis.

A dataset containing 9637 h of two-dimensional video disdrometer observations consisting of more than 240 million raindrops measured at diverse climatological locations was compiled to help characterize underlying drop size distribution (DSD) assumptions that are essential to make precise retrievals of rainfall using remote sensing platforms. This study concentrates on the tail of the DSD, which largely impacts rainfall retrieval algorithms that utilize radar reflectivity. The maximum raindrop diameter was a median factor of 1.8 larger than the mass-weighted mean diameter and increased with rainfall rate. Only 0.4% of the 1-min DSD spectra were found to contain large raindrops exceeding 5 mm in diameter. Large raindrops were most abundant at the tropical locations, especially in Puerto Rico, and were largely concentrated during the spring, especially at subtropical locations. Giant raindrops exceeding 8 mm in diameter occurred at tropical, subtropical, and high-latitude continental locations. The greatest numbers of giant raindrops were found in the subtropical locations, with the largest being a 9.7-mm raindrop that occurred in northern Oklahoma during the passage of a hail-producing thunderstorm. These results suggest large raindrops are more likely to fall from clouds that contain hail, especially those raindrops exceeding 8 mm in diameter.

Despite evidence that CABG surgery using the radial artery (RA) instead of saphenous vein (SV) grafts provide superior patency rate and outcomes, RA has been underutilised in current comparisons between CABG and PCI. We investigated whether CABG surgery using RA instead of SV grafts is a superior

An impact-type Joss–Waldvogel disdrometer (JWD), a two-dimensional video disdrometer (2DVD), and a laser optical OTT Particle Size and Velocity (PARSIVEL) disdrometer (PD) were used to measure the raindrop size distribution (DSD) over a 6-month period in Huntsville, Alabama. Comparisons indicate event rain totals for all three disdrometers that were in reasonable agreement with a reference rain gauge. In a relative sense, hourly composite DSDs revealed that the JWD was more sensitive to small drops (

Small institutional studies have shown that adrenalectomy to remove solitary metastases to the adrenal gland is safe and can improve overall survival for selective primary tumors. However, outcomes of adrenal metastasectomy have not been evaluated using large, national databases. All cases of adrenal metastasectomies from 1992 to 2011 were identified in the HCUP-NIS database. The primary endpoint analyzed was death during the same hospitalization. Secondary outcomes included length of stay (LOS), blood loss requiring transfusion, surgical infection, cardiac complications, and respiratory complications. A sub-analysis of 428 patients stratified by primary tumor (where data were available) was also performed. Statistical analysis was performed using chi-square, ANOVA, and logistic regression using Stata software, significance was set at p value of 0.05. A total of 2,057 cases of adrenal metastasectomies were identified. Median age of the patients was 62 ± 13.2 years (49.9 % men, 69.7 % Caucasian). Over the study period, there was a general increase in the number of cases performed and the number performed by minimally invasive approaches. There was also a decrease in LOS and number of deaths. However, age ≥71 years predicted a significantly higher rate of mortality (OR = 6.0, CI 1.3–26.5) when controlled for race, procedure type, year of surgery, and primary tumor in multivariable analysis. This age group had a higher number of cardiac complications (5.4 %, p = 0.005) that potentially contributed to the higher mortality rate. In addition, there was no difference in surgical outcomes when stratified by primary tumor type for the entire cohort of patients. Adrenal metastasectomy is a safe procedure with decreasing same-hospitalization mortality from 1992 to 2011. However, age ≥71 years is a significant risk factor for same-hospitalization mortality. This increased risk should be considered when discussing adrenal metastasectomy in this age population.

The response of the precipitation field for tropical cyclones in relation to the surrounding environmental vertical wind shear has been investigated using ∼20 000 snapshots of passive-microwave satellite rain rates. Composites of mean rain rates, 95th percentile rain rates, and rain coverage were constructed to compare how the spatial distribution of the precipitation was organized under varying environmental shear. Results indicated that precipitation is displaced downshear and to the left (right for Southern Hemisphere) of the shear vector. The amplitude of this displacement increases with stronger shear. The majority of the asymmetry found in the mean rain rates is accounted for by the asymmetry in the occurrence of heavy rain. Although rain is common in all quadrants of the sheared tropical cyclones, heavy rain (≥8 mm h−1 at the ∼25-km scale) is comparatively rare in the upshear-right quadrant. It is shown that the effect that shear has on the rain field is nearly instantaneous. Strong westerly shear formed slightly more asymmetric patterns than strong easterly shear.