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Restoration of lymphatic drainage across the bronchial anastomosis after lung transplantation requires several weeks. As donor antigen and antigen presenting cell trafficking via lymphatics into graft-draining lymph nodes is an important component of the alloresponse, alternative pathways must exist that account for rapid rejection after pulmonary transplantation. Here, we describe a novel allorecognition pathway mediated through donor extracellular vesicle (EV) trafficking to mediastinal lymph nodes via the pleural space. Pleural fluid collected early after lung transplantation in rats and humans contains donor-specific EVs. In a fully MHC mismatched rat model of lung transplantation, we demonstrate EVs carrying donor antigen preferentially accumulate in mediastinal lymph nodes and colocalize with MHC II expressing cells within 4 h of engraftment. Injection of allogeneic EVs into pleural space of syngeneic lung transplant recipients confirmed their selective trafficking to mediastinal lymph nodes and resulted in activation of T cells in mediastinal, but not peripheral lymph nodes. Thus, we have uncovered an alternative pathway of donor antigen trafficking where pulmonary EVs released into the pleural space traffic to locoregional lymph nodes via pleural lymphatics. This pathway obviates the need for restoration of lymphatics across the bronchial anastomosis for trafficking of donor antigen to draining lymph nodes.

Thoracic aortic aneurysm (TAA) is a significant risk factor for aortic dissection and rupture. Guidelines recommend referral of patients to a cardiovascular specialist for periodic surveillance imaging with surgical intervention determined primarily by aneurysm size. We investigated the association between socioeconomic status (SES) and surveillance practices in patients with ascending aortic aneurysms.We retrospectively reviewed records of 465 consecutive patients diagnosed between 2013 and 2016 with ascending aortic aneurysm ≥4 cm on computed tomography scans. Primary outcomes were clinical follow-up with a cardiovascular specialist and aortic surveillance imaging within 2 years following index scan. We stratified patients into quartiles using the area deprivation index (ADI), a validated percentile measure of 17 variables characterizing SES at the census block group level. Competing risks analysis was used to determine interquartile differences in risk of death before follow up with a cardiovascular specialist.Lower SES was associated with significantly lower rates of surveillance imaging and referral to a cardiovascular specialist. On competing risks regression, the ADI quartile with lowest SES had lower hazard of follow-up with a cardiologist or cardiac surgeon before death (hazard ratio: 0.46 [0.34, 0.62], p .001). Though there were no differences in aneurysm size at time of surgical repair, patients in the lowest socioeconomic quartile were more frequently symptomatic at surgery than other quartiles (92% vs. 23%-38%, p .001).Patients with lower SES receive less timely follow-up imaging and specialist referral for TAAs, resulting in surgical intervention only when alarming symptoms are already present.

Objective Overprescribing of opioids has contributed to the opioid epidemic. Electronic medical records systems can auto-populate a default number of opioid pills that are prescribed at time of discharge. The aim of this study was to examine the association between lowered default pill counts with changed prescribing practices after cardiac surgery. Methods On May 18, 2017, the default number of pills prescribers see in electronic medical records in the Yale New Haven Health System was lowered from 30 to 12. Patients undergoing coronary artery grafts, valve surgeries, and thoracic aortic aneurysm surgeries were included in this study. Data were gathered and stratified into 2 groups: 1 year before and 1 year following the default change. The amount of opioid prescribed was compared between the 2 groups. Results A total of 1741 patient charts were reviewed, 832 before the change and 909 after the change. Significant changes were seen in prescribing practices, where the average amount of opioid prescribed was about 25% lower after the change. This amounted to about 15 fewer pills of 5 mg morphine for each patient. A linear regression model adjusting for other factors determined a prescribing difference of 75.2 morphine milligram equivalents per prescription (P Conclusions Lowering the default opioid pill count in electronic medical record systems is a simple intervention that may modify prescribing behavior to promote judicious prescribing of opioids after cardiac surgery.

AimsHypoplastic left heart syndrome (HLHS) survival relies on surgical reconstruction of the right ventricle (RV) to provide systemic circulation. This substantially increases the RV load, wall stress, maladaptive remodelling, and dysfunction, which in turn increases the risk of death or transplantation.Methods and resultsWe conducted a phase 1 open-label multicentre trial to assess the safety and feasibility of Lomecel-B as an adjunct to second-stage HLHS surgical palliation. Lomecel-B, an investigational cell therapy consisting of allogeneic medicinal signalling cells (MSCs), was delivered via intramyocardial injections. The primary endpoint was safety, and measures of RV function for potential efficacy were obtained. Ten patients were treated. None experienced major adverse cardiac events. All were alive and transplant-free at 1-year post-treatment, and experienced growth comparable to healthy historical data. Cardiac magnetic resonance imaging (CMR) suggested improved tricuspid regurgitant fraction (TR RF) via qualitative rater assessment, and via significant quantitative improvements from baseline at 6 and 12 months post-treatment (P < 0.05). Global longitudinal strain (GLS) and RV ejection fraction (EF) showed no declines. To understand potential mechanisms of action, circulating exosomes from intramyocardially transplanted MSCs were examined. Computational modelling identified 54 MSC-specific exosome ribonucleic acids (RNAs) corresponding to changes in TR RF, including miR-215-3p, miR-374b-3p, and RNAs related to cell metabolism and MAPK signalling.ConclusionIntramyocardially delivered Lomecel-B appears safe in HLHS patients and may favourably affect RV performance. Circulating exosomes of transplanted MSC-specific provide novel insight into bioactivity. Conduct of a controlled phase trial is warranted and is underway.Trial registration number NCT03525418.

Anomalous origin of the left circumflex artery is a rare anatomical variant that may present a unique challenge in emergent aortic surgery.

Background The Coronavirus 19 (COVID‐19) pandemic forced an unprecedented shift of postoperative care for cardiac surgery patients to telemedicine. How patients and surgeons perceive telemedicine is unknown. We examined patient and provider satisfaction with postoperative telehealth visits following cardiac surgery. Methods Between April 2020 and September 2020, patients who underwent open cardiac surgery and had a postoperative appointment via telemedicine were administered a patient satisfaction survey over the phone. Time of survey administration ranged from 1 to 4 weeks following their appointment. Surgeons also completed a satisfaction survey following each telemedicine appointment they conducted. Results Fifty patients were surveyed. Of these, 36 (72%) had a postoperative appointment over the telephone, and 14 (28%) had a postoperative appointment via video‐chat. Overall, patients expressed satisfaction with the care that they received via our two telemedicine modalities (mean Likert scale agreement 4.8, SD 0.5). Despite this, 46% of patients said they would prefer their next postoperative appointment to be via telemedicine even if there was not a stay‐at‐home order in place. All surgeons surveyed reported (agree/strongly agree) that they would prefer to see their postoperative patients using telemedicine. Conclusions These findings highlight acceptability of continuing telemedicine use in the postoperative care of cardiac surgery patients.

Purpose Diffuse mega-aorta is challenging. Prior studies have raised concerns regarding the safety of the open two-stage elephant trunk (ET) approach for extensive thoracic aortic aneurysm (TAA), specifically in regard to interstage mortality. This study evaluates the safety of the two-stage ET approach for management of extensive TAA. Methods Between 2003 and 2018, 152 patients underwent a Stage I ET procedure by a single surgeon (mean age 64.5 ± 14.8). Second stage ET procedure was planned in 60 patients (39.4%) and to-date has been performed in 54 patients (90%). (in the remaining patients, the ET was prophylactic for the long-term, with no plan for near-term utilization). Results In-hospital mortality after the Stage I procedure was 3.3% (5/152). In patients planned for Stage II, the median interstage interval was 5 weeks (range: 0-14). Of the remaining six patients with planned, but uncompleted Stage II procedures, five patients expired from various causes in the interval period (interstage mortality of 8.3%). There were no cases of aortic rupture in the interstage interval. Stage II was completed in 58 patients (including four unplanned) with a 30-day mortality of 10.3% (6/58). Seven patients developed strokes after Stage II (12%), and three patients (5.1%) developed paraplegia. Conclusions The overall mortality, including Stage I, interstage interval, and Stage II was 18.6%. This substantial cumulative mortality for the open two-staged ET approach for the treatment of extensive TAA appears commensurate with the severity of the widespread aortic disease in this patient group. Fear of interstage rupture should not preclude the aggressive Two-Stage approach to the management of extensive TAA.

Objective Hybrid arch procedures (arch vessel debranching with thoracic endovascular aneurysm repair [TEVAR] coverage of arch pathology) have been presented as an alternative to total arch replacement (TAR). But multicenter-based analyses of these two procedures are needed to benchmark the field and establish areas of improvement. Methods The Society of Thoracic Surgeons (STS) Adult Cardiac Surgery Database from July 2014 to December 2015 was queried for elective TAR and hybrid arch procedures. Demographics and operative characteristics were compared and stepwise variable selection was used to create a risk-set used for adjustment of all multivariable models. Results A total of 1,011 patients met inclusion criteria, 884 underwent TAR, and 127 had hybrid arch procedures. TAR patients were younger (mean age: 62.7 ± 13.3 vs. 66.7 ± 11.9 years; p = 0.001) and had less peripheral vascular disease (34.0 vs. 49.6%; p Conclusion TAR remains the gold standard for elective aortic arch pathologies. Despite risk adjustment, hybrid arch procedures were associated with increased risk of mortality and stroke, advocating for careful adoption of these strategies.

(1) Background: Our goal was to develop a risk prediction model for mortality in patients with moderate and severe aortic stenosis (AS). (2) Methods: All patients aged 40–95 years, with echocardiographic evidence of moderate and severe AS at a single institution, were studied over a median of 2.8 (1.5–4.8) years, between 2013–2018. Patient characteristics and mortality were compared using Chi-squares, t-tests, and Kaplan–Meier (KM) curves, as appropriate. The risk calculation for mortality was derived using the Cox proportional hazards model. A risk score was calculated for each parameter, and the total sum of scores predicted the individualized risks of 1-and 5-year mortality. (3) Results: A total of 1991 patients with severe and 2212 with moderate AS were included. Severe AS patients were older, had a lower ejection fraction %, were more likely to be Caucasian, and had lower rates of obesity and smoking, but had higher rates of cardiac comorbidities and AVR (49.3% vs. 2.8%, p < 0.0001). The unadjusted overall mortality was 41.7% vs. 41%, p = 0.6530, and was not different using KM curves (log rank, p = 0.0853). The models included only patients with complete follow-up (3966 in the 1-year, and 816 in the 5-year model) and included 13 variables related to patient characteristics, degree of AS, and AVR. The C-statistic was 0.75 and 0.72 for the 1-year and the 5-year models, respectively. (4) Conclusions: Patients with moderate and severe AS experience high morbidity and mortality. The usage of a risk prediction model may provide guidance for clinical decision making in complex patients.

(1) Background: The clinical burden of aortic stenosis (AS) remains high in Western countries. Yet, there are no screening algorithms for this condition. We developed a risk prediction model to guide targeted screening for patients with AS. (2) Methods: We performed a cross-sectional analysis of all echocardiographic studies performed between 2013 and 2018 at a tertiary academic care center. We included reports of unique patients aged from 40 to 95 years. A logistic regression model was fitted for the risk of moderate and severe AS, with readily available demographics and comorbidity variables. Model performance was assessed by the C-index, and its calibration was judged by a calibration plot. (3) Results: Among the 38,788 reports yielded by inclusion criteria, there were 4200 (10.8%) patients with ≥moderate AS. The multivariable model demonstrated multiple variables to be associated with AS, including age, male gender, Caucasian race, Body Mass Index ≥ 30, and cardiovascular comorbidities and medications. C-statistics of the model was 0.77 and was well calibrated according to the calibration plot. An integer point system was developed to calculate the predicted risk of ≥moderate AS, which ranged from 0.0002 to 0.7711. The lower 20% of risk was approximately 0.15 (corresponds to a score of 252), while the upper 20% of risk was about 0.60 (corresponds to a score of 332 points). (4) Conclusions: We developed a risk prediction model to predict patients’ risk of having ≥moderate AS based on demographic and clinical variables from a large population cohort. This tool may guide targeted screening for patients with advanced AS in the general population.

OBJECTIVES Our aim was to evaluate clinical and neurological effects of common carotid artery (CCA) true lumen flow impairment or occlusion in patients with type A aortic dissection. METHODS Characteristics and imaging data of patients with dissected CCA secondary to acute type A aortic dissection from 3 institutions were analysed. We defined true lumen blood flow as unimpaired when the maximum true lumen diameter exceeded 50% of the complete CCA diameter, as impaired when the true lumen was compressed to ˃50% of the complete lumen, or as occluded. RESULTS Out of 440 patients, 207 presented unimpaired CCA flow, 172 impaired CCA flow and CCA occlusion was present in 61 patients. Preoperative shock (P = 0.045) or a neurological deficit (P CONCLUSIONS Shock and non-cerebral, other-organ malperfusion are common in patients with CCA dissection. While there is a high risk for stroke in patients with CCA occlusion, CCA flow impairment and occlusion were not predictive for in-hospital mortality. Surgery should not be denied to patients with CCA flow impairment or occlusion.

Background Patients with acute type A aortic dissection (ATAAD) present with heterogeneous involvement of the aortic root complex. Despite this variation, the aortic root can usually be preserved the majority of the time by Teflon (WL Gore, Newark, DE) inlay patch reconstruction of the dissected sinuses of Valsalva (SOV). In this study, we report the long term anatomic, functional, and clinical outcomes associated with the preserved SOV after surgery for ATAAD. Methods From 2002-2017, of 776 emergency ATAAD operations at a single institution, 558 (71.9%) underwent valve resuspension with SOV preservation. Echocardiography reports were reviewed to obtain postoperative SOV dimensions. Cumulative incidence of SOV dilation ≥ 4 5mm was calculated using the Fine-Gray method with death as a competing risk. Repeated-measures linear mixed effects model was used to determine risk factors for SOV growth over time. Results During the follow-up period, 62 of 558 (11.1%) patients developed SOV diameter ≥ 45 mm. Cumulative incidence of SOV dilation ≥ 45 mm at 1, 5, and 10 years was 5.5%, 12.4%, and 18.9% respectively. In a multivariable Cox regression model, preoperative SOV diameter ≥ 45 mm was associated with a hazard ratio of 14.11 (95% confidence interval 7.03-31.62) for postoperative SOV dilation ≥ 45 mm. In a repeated-measures linear mixed effects model, preoperative and discharge SOV diameter were significant predictors of SOV dilation. Postoperative time course was also identified as significant indicating growth over time. Conclusions The preserved sinuses of Valsalva after surgery for ATAAD may be prone to progressive dilatation over time. Closer echocardiographic surveillance may be warranted in these patients.

The intrahepatic milieu is inhospitable to intraportal islet allografts1–3, limiting their applicability for the treatment of type 1 diabetes. Although the subcutaneous space represents an alternate, safe and easily accessible site for pancreatic islet transplantation, lack of neovascularization and the resulting hypoxic cell death have largely limited the longevity of graft survival and function and pose a barrier to the widespread adoption of islet transplantation in the clinic. Here we report the successful subcutaneous transplantation of pancreatic islets admixed with a device-free islet viability matrix, resulting in long-term euglycaemia in diverse immune-competent and immuno-incompetent animal models. We validate sustained normoglycaemia afforded by our transplantation methodology using murine, porcine and human pancreatic islets, and also demonstrate its efficacy in a non-human primate model of syngeneic islet transplantation. Transplantation of the islet–islet viability matrix mixture in the subcutaneous space represents a simple, safe and reproducible method, paving the way for a new therapeutic paradigm for type 1 diabetes. Yu et al. report a preparation that enables transplantation of pancreatic islets underneath the skin and achieves long-term euglycaemia in several preclinical models of type 1 diabetes, thus providing a simple method that might enable a more widespread adoption of islet transplantation in the clinic.

Background Since the first reported use of prosthetic aortic grafts, infection has remained a feared complication. Pedicled omentum is the preferred flap in managing thoracic aortic graft infection (TAGI); however the literature is sparse. The authors present their experience with TAGI managed with pedicled omental flaps. Methods A single-institutional review from 2007 to 2018 was performed to analyze postoperative outcomes of omental flap reconstruction, performed by 2 surgeons, after a confirmed diagnosis of TAGI. The primary outcomes of overall complication rate, 30-day mortality, and in-hospital mortality were evaluated with univariate analysis. Results Twenty patients requiring omental flap reconstruction after TAGI met inclusion criteria. The patient cohort included 14 men and 6 women with a mean age of 60.6 ± 12.9 years and a mean Charlson comorbidity index of 3.3 ± 2.1. Nine patients (45%) received omental flap reconstruction at the time of incipient TAGI surgical management by the cardiothoracic surgery team, whereas 11 patients received delayed reconstruction (mean, 6.22 days [range, 1-27]). The most common complications were graft leak (20%) and pseudoaneurysm (25%), with only 1 patient developing recurrent infection. Overall 30-day mortality was 20%. Chronic obstructive pulmonary disease and delayed omental flap reconstruction were associated with 30-day mortality (P = .04). Four of 11 patients (36.4%) who received delayed omental flap reconstruction died within 30 days, whereas 0 of 9 patients (0%) in the immediate omental coverage group died within 30 days (P = .043). Conclusions High mortality rates associated with TAGI exemplify the challenges associated with this disease process and patient population. Pedicled omentum is a safe adjunct with promising results to the management of TAGI while significantly reducing the risk of reinfection.

Background Screening protocols do not exist for ascending thoracic aortic aneurysms (ATAAs). A risk prediction algorithm may aid targeted screening of patients with an undiagnosed ATAA to prevent aortic dissection. We aimed to develop and validate a risk model to identify those at increased risk of having an ATAA, based on readily available clinical information. Methods and Results This is a cross‐sectional study of computed tomography scans involving the chest at a tertiary care center on unique patients aged 50 to 85 years between 2013 and 2016. These criteria yielded 21 325 computed tomography scans. The double‐oblique technique was used to measure the ascending thoracic aorta, and an ATAA was defined as >40 mm in diameter. A logistic regression model was fitted for the risk of ATAA, with readily available demographics and comorbidity variables. Model performance was characterized by discrimination and calibration metrics via split‐sample testing. Among the 21 325 patients, there were 560 (2.6%) patients with an ATAA. The multivariable model demonstrated that older age, higher body surface area, history of arrhythmia, aortic valve disease, hypertension, and family history of aortic aneurysm were associated with increased risk of an ATAA, whereas female sex and diabetes were associated with a lower risk of an ATAA. The C statistic of the model was 0.723±0.016. The regression coefficients were transformed to scores that allow for point‐of‐care calculation of patients' risk. Conclusions We developed and internally validated a model to predict patients' risk of having an ATAA based on demographic and clinical characteristics. This algorithm may guide the targeted screening of an undiagnosed ATAA.

Background: Currently, there are no guidelines regarding the optimal daily timing of inpatient warfarin administration. Objective: The purpose of this study was to determine whether dosing warfarin in the morning will have a significant impact on therapeutic international normalized ratio (INR) achievement compared with evening administration in mechanical mitral valve patients initiated on warfarin following cardiac surgery. Methods: This was a single-center, pre- and post-retrospective cohort conducted between 2014 and 2018. One-hundred fifty-four adult patients who underwent a mechanical mitral valve replacement or alternative cardiac surgery with a history of a mechanical mitral valve were enrolled. The primary outcome was achievement of therapeutic INR at any time point after initiation of warfarin. Pre-intervention administration timing was 6 pm and post-intervention timing was 10 am. Results: Baseline characteristics including age, sex, and race were similar between the 2 groups ( P = NS for each characteristic). Therapeutic INR achievement was significantly improved at all time points following 10 am warfarin administration compared with 6 pm (hazard ratio = 1.69; P = .005). Mean time-to-therapeutic INR was 7.37 days in the post-intervention group and 8.39 days in the pre-intervention group ( P = .073). There were no significant differences in INR >4, bleeding, or thrombotic complications between groups. Conclusion and Relevance: This retrospective analysis suggests that there may be a postoperative benefit in therapeutic INR achievement in mechanical valve patients when dosing warfarin in the morning compared with evening administration. Large-scale studies should be conducted to further elucidate the potential benefit across more heterogeneous populations.

OBJECTIVES Volume concentration of complex noncardiac operations to high-volume centers has been observed, but whether this is also occurring in cardiac surgery is unknown. We examined the relationship between volume concentration and mortality rates for valve surgery and coronary artery bypass grafting (CABG) between 2005 and 2016 in New York State. METHODS We analyzed publicly available, hospital-level case volume and risk-adjusted mortality rates (RAMRs) from 2005 to 2016 for isolated CABG and isolated or concomitant valve operations performed in New York. We identified hospitals in the top- and bottom-volume quartiles for each procedure type and compared changes in percent market share and outcomes. Bivariate and univariate longitudinal analysis was used to evaluate the statistical significance of the temporal trend. RESULTS Among 36 centers, percent market share of the top-volume quartile increased for valve cases from 54.4% to 59.4%, whereas CABG share increased from 41.4% to 44.3%. No significant changes were noted in market share for the bottom quartile. The top-volume quartile demonstrated significant trends in improving outcomes over the study period for both valve procedures (RAMR: -0.261%/year, P

BACKGROUND Bicuspid aortic valve is the most common congenital heart defect and predisposes patients to developing aortic stenosis more frequently and at a younger age than the general population. However, the influence of bicuspid aortic valve on the rate of progression of aortic stenosis remains unclear. METHODS In 236 patients (177 tricuspid aortic valve and 59 bicuspid aortic valve) matched by initial severity of mild or moderate aortic stenosis, we retrospectively analyzed baseline echocardiogram at diagnosis with latest available follow-up echocardiogram. Baseline comorbidities, annualized progression rate of hemodynamic parameters, and hazard of aortic valve replacement were compared between valve phenotypes. RESULTS Median echocardiographic follow-up was 2.6 (interquartile range [IQR] 1.6-4.2) years. Patients with tricuspid aortic stenosis were significantly older with more frequent comorbid hypertension and congestive heart failure. Median annualized progression rate of mean gradient was 2.3 (IQR 0.6-5.0) mmHg/year versus 1.5 (IQR 0.5-4.1) mmHg/year (p = .5), and that of peak velocity was 0.14 (IQR 0-0.31) m/s/year versus 0.10 (IQR 0.04-0.26) m/s/year (p = .7) for tricuspid versus bicuspid aortic valve, respectively. On multivariate analyses, bicuspid aortic valve was not significantly associated with more rapid progression of aortic stenosis. In a stepwise Cox proportional hazards model adjusted for baseline mean gradient, bicuspid aortic valve was associated with increased hazard of aortic valve replacement (hazard ratio: 1.7, 95% confidence interval [1.0-3.0], p = .049). CONCLUSION Bicuspid aortic valve may not significantly predispose patients to more rapid progression of mild or moderate aortic stenosis. Guidelines for echocardiographic surveillance of aortic stenosis need not be influenced by valve phenotype.

OBJECTIVES Our goal was to evaluate postoperative outcomes in patients with type A aortic dissection with preoperative neurological deficits independent of shock. METHODS Between 2002 and 2017, 150 of 1600 patients, operated on for aortic dissection type A in 3 centres, presented with preoperative new onset neurological deficits. Postoperative outcomes were classified using a modified Rankin Scale (mRS) as ‘no to moderate disability’ (mRS 0–3) or as ‘poor clinical outcome’ (mRS 4–6). Clinical and radiographic data were analysed. RESULTS Ninety-three patients (62%) had no to moderate disability and 57 (38%) had a poor clinical outcome. The in-hospital mortality rate was 18% (28 patients). Patients with poor clinical outcomes were significantly older (P = 0.01) and had a significantly higher incidence of hypertension (P = 0.04), history of stroke (P = 0.03) and common carotid artery occlusion (left common carotid artery: P = 0.01; right common carotid artery: P CONCLUSIONS Most patients with preoperative neurological deficit have no to moderate disability postoperatively but commonly develop preoperative haemodynamic instability. This study suggests that an immediate surgical approach may be reasonable in patients with preoperative neurological deficit or coma.

Prior single-center studies suggest that kidney and liver allografts are immunoprotective toward transplanted hearts. The broader effects of the simultaneous transplantation of kidney or liver on protection from rejection are unclear.The United Network for Organ Sharing database for heart transplantation was queried from 1987 to 2015 and stratified into patients undergoing heart-liver transplantation (HLT) (n = 192), heart-kidney transplantation (HKT) (n = 1,174), and heart-only transplantation (HT) (n = 61,471). Perioperative and follow-up data were compared between HT versus HLT and HT versus HKT groups using analysis of variance (continuous), chi-square test (categorical), and Kaplan-Meier curves (survival).HKT patients were older (51.2 ± 13.4 years of age) compared with HT patients (45.6 ± 19.2 years of age; p0.0001), with higher rate of diabetes (33.8% versus 14.8%; p0.0001) and dialysis (49.7% versus 2.1%; p0.0001). HKT (46.2%) and HLT (49.5%) patients had more urgent need for transplantation (status 1A) compared with HT patients (32%; p0.0001). Acute rejection episodes before discharge were lower in the HLT group (7.1% versus 3.1%; p = 0.03). Ten-year patient survivals were similar for HT (53.6%) versus HKT (56.7%) (p = 0.13) versus HLT (60.4%) (p = 0.09). Treatment for rejection during the first posttransplant year was lower in HLT (2.1%) and HKT (8.4%) compared with HT (17.4%) (p0.0001 for both). Cox multivariate analysis showed that cardiac allograft survival was improved in HKT (odds ratio, 0.58; 95% confidence interval [CI], 0.49 to 0.70; p0.0001). Additionally, HKT (hazard ratio, 0.52; 95% CI, 0.45 to 0.60; p0.0001) and HLT (hazard ratio, 0.24; 95% CI, 0.15 to 0.39; p0.0001) were associated with improved freedom from rejection.Nationally, HKT and HLT have equivalent postoperative outcomes as HT. Simultaneous kidney or liver transplantation confers an improved clinical and immunologic outcome.

Background Unlike coronary artery bypass and aortic and mitral valve procedures, there is no predictive risk model for aortic root replacement procedures. As a first step toward development of a risk model, this study analyzed The Society of Thoracic Surgeons (STS) Adult Cardiac Surgery Database to determine factors predictive of mortality and morbidity in patients undergoing elective aortic root replacement (ARR). Methods The STS database was queried (from July 2011 to June 2016) for elective ARR with the following exclusion criteria: urgent or salvage cases, endocarditis, redo cardiac surgery, circulatory arrest, and aortic arch surgery. Adjusted multivariate logistic regression models for outcomes of mortality and composite STS morbidity were performed using covariates of the STS aortic valve risk set (expressed as odds ratios [ORs]). Results Of 24,244 patients undergoing ARR, 8,807 (77.6% male) met inclusion criteria in 808 centers; 33.7% (n = 2,965) had a bicuspid aortic valve, and 3.7% (n = 327) had Marfan syndrome. The median age was 58.0 years (interquartile range, 49 to 67 years). Median intensive care unit and hospital stays were 46 hours and 6 days, respectively. Significant predictors for mortality included: atrial fibrillation (OR, 2.06), body surface area (OR, 0.14), chronic obstructive pulmonary disease (OR, 1.2), New York Heart Association class IV (OR, 2.53), diabetes (OR, 2.48), coronary artery bypass grafting (OR, 2.77), mitral valve surgery (OR, ≥2.18), and Bentall operation (OR, 2.08). Regression analysis for risk factors for STS morbidity yielded 14 significant factors. A glomerular filtration rate increase of 20 units was predictive of improved mortality (OR, 0.85) and morbidity (OR, 0.91). Conclusions Elective ARR is performed with excellent postoperative outcomes. Analysis of the STS database reveals several significant risk factors that are independently associated with increased mortality and morbidity. The investigators anticipate that future studies inclusive of the nonelective ARR cases in the database will facilitate development of a risk model for root replacement procedures.

The study objective was to evaluate the safety and effectiveness of the second-generation, low-profile RelayPro (Terumo Aortic) thoracic endograft for the treatment of descending thoracic aortic aneurysm or penetrating atherosclerotic ulcer.A prospective, international, nonblinded, nonrandomized, pivotal trial analyzed a primary safety end point of major adverse events at 30 days (death, myocardial infarction, stroke, renal/respiratory failure, paralysis, bowel ischemia, procedural blood loss) and a primary effectiveness end point of treatment success at 1 year (technical success, patency, absence of aneurysm rupture, type I/III endoleaks, stent fractures, reinterventions, aneurysm expansion, and migration) compared with performance goals from the previous generation Relay pivotal study. The study was conducted in 36 centers in the United States and Japan and enrolled participants between 2017 and 2019.The study population of 110 patients had a median (interquartile range) age of 76 (70-81) years, 69 (62.7%) were male, and 43 (39.1%) were Asian. Patients were treated for 76 fusiform aneurysms (69%), 24 saccular aneurysms (22%), and 10 penetrating atherosclerotic ulcers (9%). Most patients (82.7%) were treated with a non-bare stent configuration. Technical success was 100%. The median (interquartile range) procedure time was 91 (64-131) minutes, and the deployment time was 16 (10-25) minutes. A total of 50 patients (73.5%) in the US cohort had percutaneous access, whereas centers in Japan used only surgical cutdown. The 30-day composite major adverse events rate was 6.4% (95% upper confidence interval, 11.6%; P = .0002): 2 strokes, 2 procedural blood losses greater than 1000 mL requiring transfusion, 2 paralysis events, and 1 renal failure. Primary effectiveness was 89.2% (lower 95% confidence interval, 81.8%; P = .0185). Nine subjects experienced 11 events (1 aneurysm expansion, 6 secondary interventions, and 4 type I endoleaks). There was no loss of stent-graft patency, no rupture, no fractures, and no migration.The low-profile RelayPro thoracic endograft met the study primary end points and demonstrated satisfactory 30-day safety and 1-year effectiveness for the treatment of patients with aneurysms of the descending thoracic aorta or penetrating atherosclerotic ulcers. Follow-up is ongoing to evaluate longer-term outcomes and durability.

Medial degeneration is a common histopathological finding in aortopathy and is considered a mechanism for dilatation. We investigated if medial degeneration is specific for sporadic thoracic aortic aneurysms versus nondilated aortas. Specimens were graded by pathologists, blinded to the clinical diagnosis, according to consensus histopathological criteria. The extent of medial degeneration by qualitative (semi-quantitative) assessment was not specific for aneurysmal compared to nondilated aortas. In contrast, blinded quantitative assessment of elastin amount and medial cell number distinguished aortic aneurysms and referent specimens, albeit with marked overlap in results. Specifically, the medial fraction of elastin decreased from dilution rather than loss of protein as cross-sectional amount was maintained while the cross-sectional number, though not density, of smooth muscle cells increased in proportion to expansion of the media. Furthermore, elastic lamellae did not thin and interlamellar distance did not diminish as expected for lumen dilatation, implying a net gain of lamellar elastin and intralamellar cells or extracellular matrix during aneurysmal wall remodeling. These findings support the concepts that: (1) medial degeneration need not induce aortic aneurysms, (2) adaptive responses to altered mechanical stresses increase medial tissue, and (3) greater turnover, not loss, of mural cells and extracellular matrix associates with aortic dilatation.

AngioVac suction embolectomy is recommended by the manufacturer to be performed with a centrifugal pump due to safety considerations. However, roller head pumps are significantly cheaper to use, and thus may be more readily available during shortages and in resource poor settings. We present the technique of Angiovac suction embolectomy being successfully performed with a roller pump to evacuate a clot-in-transit in the inferior vena cava and right atrium, along with discussion of important safety caveats.

Bacterial outer membrane vesicles (OMVs) enriched with bioactive proteins, toxins, and virulence factors play a critical role in host-pathogen and microbial interactions. The two-component system PhoP-PhoQ (PhoPQ) of Salmonella enterica orchestrates the remodeling of outer membrane lipopolysaccharide (LPS) molecules and concomitantly upregulates OMV production. In this study, we document a novel use of nanoparticle tracking analysis to determine bacterial OMV size and number. Among the PhoPQ-activated genes tested,; pagC; expression had the most significant effect on the upregulation of OMV production. We provide the first evidence that PhoPQ-mediated upregulation of OMV production contributes to bacterial survival by interfering with complement activation. OMVs protected bacteria in a dose-dependent manner, and bacteria were highly susceptible to complement-mediated killing in their absence. OMVs from bacteria expressing PagC bound to complement component C3b in a dose-dependent manner and inactivated it by recruiting complement inhibitor Factor H. As we also found that Factor H binds to PagC, we propose that PagC interferes with complement-mediated killing of Salmonella in the following two steps: first by engaging Factor H, and second, through the production of PagC-enriched OMVs that divert and inactivate the complement away from the bacteria. Since PhoPQ activation occurs intracellularly, the resultant increase in PagC expression and OMV production is suggested to contribute to the local and systemic spread of Salmonella released from dying host cells that supports the infection of new cells.; IMPORTANCE; Bacterial outer membrane vesicles (OMVs) mediate critical bacterium-bacterium and host-microbial interactions that influence pathogenesis through multiple mechanisms, including the elicitation of inflammatory responses, delivery of virulence factors, and enhancement of biofilm formation. As such, there is a growing interest in understanding the underlying mechanisms of OMV production. Recent studies have revealed that OMV biogenesis is a finely tuned physiological process that requires structural organization and selective sorting of outer membrane components into the vesicles. In Salmonella, outer membrane remodeling and OMV production are tightly regulated by its PhoPQ system. In this study, we demonstrate that PhoPQ-regulated OMV production plays a significant role in defense against host innate immune attack. PhoPQ-activated PagC expression recruits the complement inhibitor Factor H and degrades the active C3 component of complement. Our results provide valuable insight into the combination of tools and environmental signals that Salmonella employs to evade complement-mediated lysis, thereby suggesting a strong evolutionary adaptation of this facultative intracellular pathogen to protect itself during its extracellular stage in the host.