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Background: Evolving trends in organ procurement and technological innovation prompted an investigation into recent trends, indications, and outcomes following combined heart-lung transplantation (HLTx)., Methods: The United Network for Organ Sharing database was queried for all adult (≥18 years) HLTx performed between July 1, 2013 and June 30, 2023. Patients with previous transplants were excluded. The primary endpoint was the effect of donor, recipient, and transplantation characteristics on 1- and 5-year survival. Secondary analyses included a comparison of HLTx at high- and low-volume centers, an assessment of HLTx following donation after circulatory death (DCD), and an evaluation of HLTx volume over time. Cox proportional-hazards models were used to assess factors associated with mortality. Temporal trends were evaluated with linear regression., Results: After exclusions, 319 patients were analyzed, of whom 5 (1.6%) were DCD. HLTx volume increased from 2013 to 2023 (p < 0.001). One- and 5-year survival following HLTx was 84.0% and 59.5%, respectively. One-year survival was higher for patients undergoing HLTx at a high-volume center (88.3% vs. 77.9%; p = 0.012). After risk adjustment, extracorporeal membrane oxygenation support 72 h posttransplant and predischarge dialysis were associated with increased 1-year mortality (HR = 3.19, 95% CI = 1.86-5.49 and HR = 3.47, 95% CI = 2.17-5.54, respectively) and 5-year mortality (HR = 2.901, 95% CI = 1.679-5.011 and HR = 3.327, 95% CI = 2.085-5.311, respectively), but HLTx at a high-volume center was not associated with either., Conclusions: HLTx volume has resurged, with DCD HLTx emerging as a viable procurement strategy. Factors associated with 1- and 5-year survival may be used to guide postoperative management following HLTx., (© 2024 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: Airway stenting may be needed to manage anastomotic complications in lung transplant recipients. Conventional stenting strategies may be inadequate due to anatomic variations between the recipient and donor or involvement of both the anastomosis and lobar bronchi., Methods: We investigated the efficacy of 3D-designed patient-specific silicone Y-stents in managing this scenario. 9 patients with complex airway stenosis underwent custom stent insertion after either failing traditional management strategies or having anatomy not suitable for conventional stents. CT images were uploaded to stent design software to make a virtual stent model. 3D printing technology was then used to make a mold for the final silicone stent which was implanted via rigid bronchoscopy. Forced expiratory volume in 1 s (FEV1) was measured pre- and post-stent placement., Results: 78 % of patients experienced an increase in their FEV1 after stent insertion, (p = 0.001, 0.02 at 30 and 90 days respectively). Unplanned bronchoscopies primarily occurred due to mucous plugging. 2 patients had sufficient airway remodeling allowing for stent removal., Conclusions: Personalized 3D-designed Y-stents demonstrate promising results for managing complicated airway stenosis, offering improved lung function and potential long-term benefits for lung transplant recipients., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: Surgical outcomes have been linked to the technical and cognitive abilities of an exhausted surgical team. In parallel, advancements in preservation have led to the proposal of daytime lung transplants. We sought to investigate whether time of day is associated with outcomes in lung transplants., Methods: Data on 30,404 lung transplants from 2005 to 2021 were obtained from the United Network for Organ Sharing database. Patients were categorized based on the time of surgery with "early-hours" defined as donor cross-clamp between 10PM and 3AM, and Cox regression models for 90-day and long-term mortality were made to assess the risk according to time of transplant and covariates. Additionally, the Cox modeling was repeated with donor cross-clamp and the estimated reperfusion time of day as continuous functions., Results: Among 30,404 transplants, 20.7% (6,295) were performed during "early-hours". No significant difference was found between the two groups in unadjusted 90-day and long-term mortality (log-rank, p=0.176 and 0.363), and results were unchanged when adjusting for covariates (P=0.233 and 0.738). However, when examining donor cross-clamp time and reperfusion time as continuous variables in separate multivariable analyses, we observed significant associations with 90-day mortality (P=0.002 and 0.022). Notably, lower mortality rates were observed for donor clamp-times between 8AM to 1PM and estimated reperfusion times between 1PM to 6PM., Conclusions: Although binary categorizations of the time of day of lung transplants did not show a significant impact on short- or long-term survival, continuous-time analyses demonstrated certain times during the day were associated with favorable short-term survival., (Copyright © 2024. Published by Elsevier Inc.)

Axillary artery intra-aortic balloon pump (axIABP) placement has been implemented as a bridging solution before heart transplantation. This study evaluates complications associated with axIABP support and describes an approach to minimize adverse events. We previously described a percutaneous approach for axIABP placement. However, patients receiving axIABP between September 1, 2017, and September 26, 2019 (n = 32) demonstrated a high rate of balloon pump malfunction (8/32; 25%) and other complications (totaling 15/32; 47%). Sixty-four patients were sequentially treated under a revised protocol. Compared to the initial cohort, no significant differences in demographics were noted. A significant reduction in rate of balloon malfunction (8/32, 25% vs. 1/64, 2%; p < 0.001) and total complications (15/32, 47% vs. 10/64, 16%; p = 0.0025) during the period of support were noted after intervention. Subsequent analysis of total complications per device size (40 vs. ≤ 34 ml balloon) revealed significantly reduced complications in patients with smaller devices (40% vs. 13%, respectively; p = 0.0022). This study provides guidelines to limit complications in patients supported with axIABP, facilitating a protracted period of bridging support., Competing Interests: Disclosure: The authors have no relevant conflicts of interest to report., (Copyright © ASAIO 2024.)

Background: Gastrointestinal bleeding (GIB) in patients with continuous flow left ventricular assist devices (CF-LVADs) is often related to GI angiodysplasia (GIAD). We previously reported data on VEGF inhibition with IV bevacizumab in the treatment of LVAD-associated GIAD bleeding, and now present follow-up data on patients treated with IV bevacizumab and/or low-dose oral pazopanib., Methods: All consecutive adult patients with LVAD-associated GIB from GIAD treated with bevacizumab or pazopanib, from July 20, 2017 to June 22, 2022, were included in the analysis. Data on hospitalizations, GI endoscopic procedures, and blood transfusions were obtained from first admission for GIB up to a median of 35.7 months following treatment initiation (range 1.3-59.8 months)., Results: Eleven patients (91% male, mean 69.5 ± 8.9 years) were included. Eight patients (73%) received IV bevacizumab, two patients (18%) received oral pazopanib, and one patient (9%) received bevacizumab followed by pazopanib therapy. We observed a significantly decreased number of annualized hospitalizations for GIB (median difference - 2.87, p = 0.002), blood transfusions (median difference - 20.9, p = 0.01), and endoscopies (median difference - 6.95, p = 0.007) in patients pre- and post-anti-angiogenic therapy (bevacizumab and/or pazopanib). Similarly, a significant improvement in these clinical outcomes was noted in the bevacizumab group with decreased annualized hospitalizations (median difference - 2.75, p = 0.014), blood transfusions (median difference - 24.5, p = 0.047), and number of endoscopies (median differences -6.88, p = 0.006)., Conclusion: Anti-angiogenic therapy with IV bevacizumab and/or low-dose oral pazopanib appears to provide benefits in patients with LVAD-associated GIB with reduced hospitalizations, blood transfusions, and need for GI endoscopic procedures., (© 2023 International Center for Artificial Organ and Transplantation (ICAOT) and Wiley Periodicals LLC.)

The purpose of this study was to evaluate left ventricular (LV) unloading strategies in patients supported with peripheral venoarterial extracorporeal membrane oxygenation (VA-ECMO). A retrospective review was conducted of all consecutive patients requiring VA-ECMO support for any indication, who underwent novel LV unloading strategies with either direct left atrial venoarterial (LAVA) cannulation or pulmonary artery venoarterial (PAVA) venting, in comparison to Impella and intra-aortic balloon pump (IABP). The primary outcome was successful bridge to transplant, LV assist device, or myocardial recovery. Forty-six patients (63% male, mean age 52.8 ± 17.6 years) were included. Fourteen patients (30%) underwent novel unloading with either LAVA or PAVA, 11 patients (24%) underwent IABP placement, and 21 patients (46%) underwent Impella insertion. In the novel LV unloading cohort, 10 patients (71%) survived to hospital discharge. Four patients (29%) were weaned from ECMO and eight patients (57%) underwent cardiac transplantation. Although a trend favoring cannula-based unloading for the primary outcome was noted, the cohort was too small for statistical significance (79% LAVA/PAVA, 57% Impella, 45% IABP; p = 0.21). However, probability of survival was greater in the LAVA/PAVA cohort compared to Impella and IABP ( p < 0.05). Thus, we demonstrate the efficacy of LA and PA cannulation as an alternative LV unloading strategy for patients supported with peripheral VA-ECMO., Competing Interests: Disclosure: The authors have no conflicts of interest to report., (Copyright © ASAIO 2024.)

Combined heart-lung transplant (HTLx) is the most durable treatment available for end-stage heart and lung failure. Many patients are unable to receive combined organs due to organ availability and allocation policies prioritizing separate heart or lung transplantation. While an average of 45 HTLxs have been performed per year in the United States half the listed patients do not receive organs. Recently, donation after circulatory death (DCD) utilizing normothermic regional perfusion (NRP) has been utilized for heart allografts with excellent results, and here, we present a case utilizing mobile NRP to procure a heart and lung block from a circulatory death donor and successful implantation for a recipient in a separate center., Competing Interests: Disclosure: The authors have no conflicts of interest to report., (Copyright © ASAIO 2023.)

Objective: Innovative technology such as normothermic regional perfusion and the Organ Care System has expanded donation after circulatory death heart transplantation. We wanted to investigate the impact of donation after circulatory death heart procurement in concurrent lung donation and implantation at a national level., Methods: We reviewed the United Network for Organ Sharing database for heart donation between December 2019 and March 2022. Donation after circulatory death donors were separated from donation after brain death donors and further categorized based on concomitant organ procurement of lung and heart, or heart only., Results: A total of 8802 heart procurements consisted of 332 donation after circulatory death donors and 8470 donation after brain death donors. Concomitant lung procurement was lower among donation after circulatory death donors (19.3%) than in donation after brain death donors (38.0%, P  < .001). The transplant rate of lungs in the setting of concomitant procurement is 13.6% in donation after circulatory death, whereas it is 38% in donation after brain death ( P  < .001). Of the 121 lungs from 64 donation after circulatory death donors, 22 lungs were retrieved but discarded (32.2%). Normothermic regional perfusion was performed in 37.3% of donation after circulatory death donors, and there was no difference in lung use between normothermic regional perfusion versus direct procurement and perfusion (20.2% and 18.8%). There was also no difference in 1-year survival between normothermic regional perfusion and direct procurement and perfusion., Conclusions: Although national use of donation after circulatory death hearts has increased, donation after circulatory death lungs has remained at a steady state. The implantation of lungs after concurrent procurement with the heart remains low, whereas transplantation of donation after circulatory death hearts is greater than 90%. The use of normothermic regional perfusion lungs has been controversial, and we report comparable 1-year outcomes to standard donation after circulatory death lungs. Further studies are warranted to investigate the underlying mechanisms of normothermic regional perfusion on lung function., (© 2023 The Author(s).)

Mechanical circulatory support is increasingly being used as bridge-to-transplant and destination therapy in patients with advanced heart failure. Technologic improvements have led to increased patient survival and quality of life, but infection remains one of the leading adverse events following ventricular assist device (VAD) implantation. Infections can be classified as VAD-specific, VAD-related, and non-VAD infections. Risk of VAD-specific infections, such as driveline, pump pocket, and pump infections, remains for the duration of implantation. While adverse events are typically most common early (within 90 days of implantation), device-specific infection (primarily driveline) is a notable exception. No diminishment over time is seen, with event rates of 0.16 events per patient-year in both the early and late periods postimplantation. Management of VAD-specific infections requires aggressive treatment and chronic suppressive antimicrobial therapy is indicated when there is concern for seeding of the device. While surgical intervention/hardware removal is often necessary in prosthesis-related infections, this is not so easily accomplished with VADs. This review outlines the current state of infections in patients supported with VAD therapy and discusses future directions, including possibilities with fully implantable devices and novel approaches to treatment., Competing Interests: Disclosure: The authors have no conflicts of interest to report., (Copyright © ASAIO 2023.)

Extracorporeal membrane oxygenation is used as a bridge to transplant (ECMO-BTT) in selected patients. The objective of this study was to determine whether 1-year post-transplant and post-ECMO survival are impacted by traditional compared to expanded selection criteria. We performed a retrospective study of patients >17 years who received ECMO as bridge to transplant (BTT) or bridge to transplant decision for lung or combined heart and lung transplantation at the Mayo Clinic Florida and Rochester. Institutional protocol excludes patients >55 years, maintained on steroids, unable to participate in physical therapy, with body mass index >30 or <18.5 kg/m 2 , non-pulmonary end-organ dysfunction, or unmanageable infections from ECMO-BTT. For this study, adherence to this protocol was considered traditional whereas exceptions to the protocol were considered expanded selection criteria. A total of 45 patients received ECMO as bridge therapy. Out of those 29 patients (64%) received ECMO as bridge to transplant and 16 patients (36%) as bridge to transplant decision. The traditional criteria cohort consisted of 15 (33%) patients and expanded criteria cohort consisted of 30 (67%) patients. In the traditional cohort, 9 (60%) of 15 patients were successfully transplanted compared to 16 (53%) of 30 patients in the expanded criteria cohort. No difference in being delisted or dying on the waitlist (OR: 0.58, CI: 0.13-2.58), surviving to 1-year post-transplant (OR: 0.53, CI: 0.03-9.71) or 1-year post-ECMO (OR: 0.77, CI: 0.0.23-2.56) was observed between the traditional criteria and expanded criteria cohorts. At our institution, we did not see differences in odds of 1-year post-transplant and post-ECMO survival between those who met traditional criteria compared to those who did not. Multicenter, prospective studies are needed to evaluate the impact of ECMO-BTT selection criteria., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://jtd.amegroups.com/article/view/10.21037/jtd-23-13/coif). The authors have no conflicts of interest to declare., (2023 Journal of Thoracic Disease. All rights reserved.)

Although continuous-flow left ventricular assist devices (CF-LVADs) provide an augmentation in systemic perfusion, there is a scarcity of in vivo data regarding systemic pulsatility on support. Patients supported on CF-LVAD therapy (n = 71) who underwent combined left/right catheterization ramp study were included. Aortic pulsatility was defined by the pulsatile power index (PPI), which was also calculated in a cohort of high-output heart failure (HOHF, n = 66) and standard HF cohort (n = 44). PPI was drastically lower in CF-LVAD-supported patients with median PPI of 0.006 (interquartile range [IQR], 0.002-0.012) compared with PPI in the HF population at 0.09 (IQR, 0.06-0.17) or HOHF population at 0.25 (IQR, 0.13-0.37; p < 0.0001 among groups). With speed augmentation during ramp, PPI values fell quickly in patients with higher PPI at baseline. PPI correlated poorly with left ventricular ejection fraction (LVEF) in all groups. In CF-LVAD patients, there was a stronger correlation with LV dP/dt (r = 0.41; p = 0.001) than LVEF (r = 0.21; p = 0.08; pint < 0.001). CF-LVAD support is associated with a dramatic reduction in arterial pulsatility as measured by PPI relative to HOHF and HF cohorts and decreases with speed. Further work is needed to determine the applicability to the next generation of device therapy., Competing Interests: Disclosure: The authors have no conflicts of interest to report., (Copyright © ASAIO 2022.)

The effects of left ventricular unloading on septal function in patients with left ventricular assist devices (LVADs) have not been well characterized in vivo. The purpose of this study was to evaluate the relationship between markers of septal function with echocardiography in relationship to RV dysfunction and late RV failure after LVAD implantation. A retrospective study was conducted of patients supported on centrifugal-flow LVADs implanted over a 10-year period. Echocardiographic data were collected pre-operatively and up to 2 years after implantation. Interventricular septum (IVS) measurements were taken at end-systole and end-diastole. Interventricular-septal output (ISO) was calculated using the formula: (IVSs-IVSd)×heart rate. A total of 110 patients were included. An immediate and sustained reduction in both lateral annulus systolic velocity (RVS') and TAPSE were observed after implant ( p < 0.0001). However, ISO gradually decreased over time ( p < 0.0001). While ISO was not predictive of late RV failure, a decrease in ISO by 25% or greater from pre-implant to hospital discharge was associated with late RV failure (OR 4.8; 95% CI, 1.4-16.5; p = 0.012) even after adjusting for relevant clinical variables ( p ≤ 0.01 for each model). RV function is known to be influenced by mechanical ventricular interdependence and we demonstrate that measurement of ISO may be a useful marker in assessing RV dysfunction and predicting RV failure in patients following LVAD implantation., Competing Interests: There are no conflicts of interest to disclose and no sources of funding., (Copyright © ASAIO 2022.)

Background: During the COVID-19 pandemic, efforts to maintain solid-organ transplantation have continued, including the use of SARS-CoV-2-positive heart donors., Methods: We present our institution's initial experience with SARS-CoV-2-positive heart donors. All donors met our institution's Transplant Center criteria, including a negative bronchoalveolar lavage polymerase chain reaction result. All but 1 patient received postexposure prophylaxis with anti-spike monoclonal antibody therapy, remdesivir, or both., Results: A total of 6 patients received a heart transplant from a SARS-CoV-2-positive donor. One heart transplant was complicated by catastrophic secondary graft dysfunction requiring venoarterial extracorporeal membrane oxygenation and retransplant. The remaining 5 patients did well postoperatively and were discharged from the hospital. None of the patients had evidence of COVID-19 infection after surgery., Conclusion: Heart transplants from SARS-CoV-2 polymerase chain reaction-positive donors are feasible and safe with adequate screening and postexposure prophylaxis., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: The COVID-19 pandemic has led to a boom in the use of V-V ECMO for ARDS secondary to COVID. Comparisons of outcomes of ECMO for COVID to ECMO for influenza have emerged. Very few comparisons of ECMO for COVID to ECMO for ARDS of all etiologies are available., Objectives: To compare clinically important outcome measures in recipients of ECMO for COVID to those observed in recipients of ECMO for ARDS of other etiologies., Methods: V-V ECMO recipients between March 2020 and March 2022 consisted exclusively of COVID patients and formed the COVID ECMO group. All patients who underwent V-V ECMO for ARDS between January 2014 and March 2020 were eligible for analysis as the non-COVID ECMO comparator group. The primary outcome was survival to hospital discharge. Secondary outcomes included ECMO decannulation, ECMO duration >30 days, and serious complications., Results: Thirty-six patients comprised the COVID ECMO group and were compared to 18 non-COVID ECMO patients. Survival to hospital discharge was not significantly different between the two groups (33% in COVID vs. 50% in non-COVID; p = 0.255) nor was there a significant difference in the rate of non-palliative ECMO decannulation. The proportion of patients connected to ECMO for >30 days was significantly higher in the COVID ECMO group: 69% vs. 17%; p = 0.001. There was no significant difference in serious complications., Conclusion: This study could not identify a statistically significant difference in hospital survival and rate of successful ECMO decannulation between COVID ECMO and non-COVID ECMO patients. Prolonged ECMO may be more common in COVID. Complications were not significantly different., Competing Interests: Declaration of Competing Interest None of the authors has any relevant competing interest to disclose., (Copyright © 2022. Published by Elsevier Inc.)

Background: Heart donation after donor brain death from cardiac arrest despite successful resuscitation may be associated with worse recipient outcomes due to potential graft ischemia or underlying rhythmic/structural defects. However, selected grafts from such donors often have normal cardiac function and anatomy. We investigated whether a cardiovascular mechanism of donor brain death (CV-DBD) was associated with worse recipient outcomes., Methods: We queried the United Network for Organ Sharing (UNOS) database for first-time, single-organ, adult (age 18+) heart transplant recipients and their associated donors between January 2005 and March 2021. Recipients were stratified by donor status (CV-DBD vs. non-CV-DBD). We performed multivariable Cox proportional hazards modeling to ascertain whether receiving a CV-DBD graft was independently associated with mortality., Results: Of 35,833 included recipients, 2,702 (7.5%) received CV-DBD grafts. The associated donors were significantly more likely to be female, older, and have a history of diabetes, hypertension, and substance use (all p < .001). On unadjusted Kaplan-Meier analysis, CV-DBD recipients had a significantly reduced median survival than non-CV-DBD recipients (12.0 vs. 13.1 years, log-rank p = .04). However, after adjusting for donor/recipient age, recipient comorbidities, annualized center volume, and transplantation era, CV-DBD organ status was not associated with recipient mortality (hazard ratio: 1.05, 95% confidence interval: 0.96-1.13, p = .28)., Conclusion: In this analysis of over 35,000 heart transplants, CV-DBD status was not associated with adjusted recipient survival. Donor brain death due to cardiac arrest should not be an absolute contraindication to heart donation, although graft function should be carefully assessed before transplantation., (© 2022 Wiley Periodicals LLC.)

We present our institution's protocol for evaluating and transplanting thoracic organs from COVID-19 positive donors and report the outcomes to date. Hearts from donors testing positive for COVID-19 on any test were eligible for transplantation at our institution provided the donor exhibited no evidence of hypercoagulability or COVID-19 induced hyperinflammatory state during terminal hospitalization. Lungs were eligible if the donor first tested PCR positive on nasopharyngeal swab (NPS) for COVID-19 > 20 days prior to procurement and had a negative lower respiratory tract specimen. We performed 14 thoracic transplants in 13 recipients using organs from COVID-19 positive donors. None of the recipients or healthcare members acquired COVID-19. No recipients suffered unexpected acute rejection. Patient survival is 92% to date, with graft survival 93%. The use of hearts from COVID-19 positive donors may be safe and effective. Transplantation of lungs is unresolved but may be cautiously pursued under the restricted circumstances., (Copyright © 2022 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.)

Objectives: Approximately 10% of lung transplant recipients have had previous cardiothoracic surgery. We sought to determine if previous surgery affects outcomes after lung transplant at a national level., Methods: The United Network for Organ Sharing database was analysed from 2005 to 2019 to include adult patients who underwent lung transplant who had previous cardiac surgery and previous thoracic surgery. T-test and chi-squared analysis were used to compare perioperative outcomes. Long-term survival comparison was performed using the Kaplan-Meier method in an unadjusted and propensity-matched analysis., Results: Out of 24 784 lung transplants, 691 (2.7%) had previous cardiac surgery and 1321 (6.5%) had previous thoracic surgery. Operative mortality was worse in previous cardiac surgery [42 (6.1%)] versus no previous cardiac surgery [740 (3.1%), P < 0.001] and in previous thoracic surgery [65 (4.9%)] versus no previous thoracic surgery [717 (3.1%), P < 0.001]. The previous thoracic surgery group had more primary graft failure and treated rejection during the first-year post-transplant. There was no difference in stroke, dialysis, intubation and extracorporeal membrane oxygenation at 72 h. Long-term survival was significantly worse for lung transplant patients who had undergone previous cardiac surgery (median 3.8 vs 6.3 years, P < 0.001) due to an increase in cardiovascular deaths (P = 0.008) and malignancy (P = 0.043). However, there was no difference in previous thoracic surgery (median 6.6 vs 6.1 years, P = 0.337)., Conclusions: Previous cardiac surgery prior to lung transplant results in worse survival related to cardiovascular death and malignancies. Previous thoracic surgery worsens perioperative outcomes but does not affect long-term survival., (© The Author(s) 2022. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.)

Massive pulmonary embolism (MPE) is associated with a 20-50% mortality rate with guideline directed therapy. MPE treatment with surgical embolectomy (SE) or venoarterial extracorporeal membrane oxygenation (VA-ECMO) have shown promising results. In the context of a surgical management strategy for MPE, a comparison of outcomes associated with VA-ECMO or SE was performed. A retrospective review of a single institution cardiac surgery database was performed, identifying MPE treated with SE or VA-ECMO between 2005-2020. Primary outcome was in-hospital survival. 59 MPE [27 (46.8%) VA-ECMO vs 32 (54.2%) SE] were identified. All presented with elevated cardiac biomarkers, tachycardia (mean heart rate 113 ± 20 beats/minute), hypotension (mean systolic blood pressure 85 ± 22 mm Hg) and vasopressors requirement, without significant differences between cohorts. Preoperative CPR was performed in 37.3% (22/59), without a significant difference between cohorts. More VA-ECMO presented with questionable neurologic status (GCS ≤ 4) [9/27 (33.3%) vs 2/32 (6.2%), P = 0.008] and more VA-ECMO failed thrombolysis [8/27 (29.6) vs 2/32 (6.3), P = 0.014]. All presented with severe RV dysfunction, by discharge all had normalization of echocardiographic RV function. Overall mortality was 10.2%, with a trend toward higher mortality among VA-ECMO [14.9% (4/27) vs 6.3% (2/32) P = 0.14]. CPR was independently associated with death (OR 10.8, P = 0.02) whereas treatment modality was not (OR 0.24). In an extremely unstable MPE population VA-ECMO and SE were safely performed with low mortality while achieving RV recovery. Adverse outcomes were more closely associated with preoperative CPR than with treatment modality., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Objective: To determine characteristics, outcomes, and clinical factors associated with death in patients with COVID-19 requiring extracorporeal membrane oxygenation (ECMO) support., Methods: A multicenter, retrospective cohort study was conducted. The cohort consisted of adult patients (18 years of age and older) requiring ECMO in the period from March 1, 2020, to September 30, 2020. The primary outcome was in-hospital mortality after ECMO initiation assessed with a time to event analysis at 90 days. Multivariable Cox proportional regression was used to determine factors associated with in-hospital mortality., Results: Overall, 292 patients from 17 centers comprised the study cohort. Patients were 49 (interquartile range, 39-57) years old and 81 (28%) were female. At the end of the follow-up period, 19 (6%) patients were still receiving ECMO, 25 (9%) were discontinued from ECMO but remained hospitalized, 135 (46%) were discharged or transferred alive, and 113 (39%) died during the hospitalization. The cumulative in-hospital mortality at 90 days was 42% (95% confidence interval [CI], 36%-47%). Factors associated with in-hospital mortality were age (adjusted hazard ratio [aHR], 1.31; 95% CI, 1.06-1.61 per 10 years), renal dysfunction measured according to serum creatinine level (aHR, 1.21; 95% CI, 1.01-1.45), and cardiopulmonary resuscitation before ECMO placement (aHR, 1.87; 95% CI, 1.01-3.46)., Conclusions: In patients with severe COVID-19 necessitating ECMO support, in-hospital mortality occurred in fewer than half of the cases. ECMO might serve as a viable modality for terminally ill patients with refractory COVID-19., (Copyright © 2021 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.)

Background: This study assessed the safety of direct axillary artery (AX) cannulation for acute type A dissection (ATAD) repair, including the impact of innominate artery dissection (IAD)., Methods: Of 281 consecutive patients who underwent ATAD repair from 2007 to 2020, preoperative computed tomography was available in 200 (IAD, n = 101; non-IAD, n = 99). IAD with compromised true lumen was defined as dissection in which the false lumen was greater than 50% of the IA diameter (n = 75 of 101)., Results: AX cannulation was attempted in 188 patients (94.0%), with a 1.6% vascular injury rate (3 patients), comprising bypass to the distal AX in 2 patients and local dissection in 1 patient. Deep hypothermic circulatory arrest was used for the distal repair in 89.5% of patients. Right AX cannulation was used in 80.2% of patients with IAD and in 88.9% without IAD (P = .075). Patients with IAD had more cerebral (21.8% vs 5.1%, P = .001) and arm malperfsion (11.9% vs 4.0%, P = .075). Operative death and stroke were comparable between non-IAD (8.1% vs 7.9%, P = 1.00) and IAD (4.0% vs 5.3%, P = .689) groups. The right AX was successfully used in 77.3% of IAD patients with a compromised true lumen, with comparable hospital outcomes to noncompromised IAD patients. Upper extremity malperfusion, multiorgan malperfusion, low ejection fraction, and female sex were predictors for noncannulation of the right AX., Conclusions: Routine direct AX cannulation strategy is safe in ATAD repair. Right AX cannulation can be used in most patients with IAD, even with a compromised true lumen, with low mortality, stroke, and vascular injury rates., (Copyright © 2022 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Background: This study reviews the outcomes of our reoperative total arch repair technique using a trifurcated graft and selective antegrade cerebral perfusion., Methods: Fifty patients underwent reoperative total arch repair from January 2005 to September 2020, with either a one-stage repair (n = 9) or two-stage repair (n = 41). The two-stage technique includes minimal dissection of the mediastinal structures, an arch-first technique using a trifurcated graft, and construction of a classical elephant trunk through a partial transverse incision distally in the old graft or in the aorta just distal to the old graft., Results: The median age was 63 years. Chronic dissection was the most frequent indication (88%), and 98% had undergone a previous proximal aortic repair at a median interval of 3 years. The median cardiopulmonary bypass, myocardial ischemic, selective antegrade cerebral perfusion, and lower body circulatory arrest times were 226, 103, 97, and 98 minutes, respectively. The minimum nasopharyngeal and bladder temperature were 16.5°C and 20.0°C, respectively. Operative mortality was 2%, the incidence of stroke was 2%, and the incidence of spinal cord injury was 0%. Stage II repair was performed in 37 patients (open, 33 patients; endovascular, 4 patients), with 2 mortalities and no spinal cord injury. The median duration between stage I and II was 63 days. Survival and aortic event free rates at 3 years were 88.4% ± 4.9%, and 89.8% ± 5%, respectively., Conclusions: We report a reoperative total arch repair technique that minimizes dissection of the cardiac structures, simplifies the distal anastomosis, and protects vital organs, such as the brain, heart, and spinal cord., (Copyright © 2022 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Faced with ageing infrastructure and ever-increasing demands from hit discovery and lead optimisation functions, AstraZeneca has chosen to develop innovative technologies and process solutions to support the future of drug discovery. These include the miniaturisation of compound storage tubes for high-density storage and rapid access to the corporate collection for feeding samples to the predicted tripling number of high throughput screening (HTS) campaigns. The acoustically- compatible tubes also enable the first fully-acoustic plate production process for faster sample supply to screening with less waste and continued high quality. Operating at a smaller scale reduces compound synthesis, storage, and consumption, prompting miniaturisation of upstream chemistry and downstream biological assays, while offering a transformative and sustainable solution to many drug discovery issues applicable across the industry., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Background: The clinical response to postoperative complications after lung transplantation (LTx) may contribute to mortality differences among transplantation centers. The ability to avoid mortality after a complication-failure to rescue (FTR)-may be an effective quality metric in LTx., Methods: The United Network for Organ Sharing database was queried for adult, first-time, lung-only transplantations from May 2005 to December 2015. Transplantation centers were stratified into equal-sized terciles on the basis of observed operative mortality rates. Several postoperative complications were identified, including stroke, acute rejection, acute kidney injury requiring hemodialysis, airway dehiscence, and extracorporeal membrane oxygenation 72 hours after surgery. Rates of FTR were calculated as the number of operative mortalities in patients who had complications divided by the number of patients who had any postoperative complications., Results: Our study population included 16,411 LTx operations performed at 69 transplantation centers. LTx centers were stratified into terciles with average perioperative mortality of 4.0% for low-mortality centers, 6.9% for intermediate-mortality centers, and 12.4% for high-mortality centers. Low-mortality centers had slightly lower complication rates (low, 15.0% vs intermediate, 17.1% vs high, 19.1%; P < .001). Differences in FTR rate were significantly more pronounced (low, 14.9% vs intermediate, 23.9% vs high, 34.2%; P < .001). Multivariable logistic regression and generalized linear models demonstrated an independent association between high FTR rates and high mortality in LTx (P < .001)., Conclusions: Differences in rates of FTR contribute significantly to per-center variability in mortality after LTx. FTR can serve as a quality metric to identify opportunities for improvement in management of perioperative adverse events., (Copyright © 2020 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Background: Lung transplants from donation after circulatory death (DCD) have been scarcely used in the United States. Concerns about the warm ischemic injury, resource mal-utilization due to the uncertain timing of death, and public scrutiny may be some factors involved., Methods: Survival for recipients of a donation after brain death (DBD) versus DCD was analyzed by using the United Network for Organ Sharing and our institutional database. A propensity-matching and Cox regression analysis was performed for 25 characteristics. Primary graft dysfunction metrics were compared., Results: A total of 389 of 20,905 lung transplantations (2%) were performed by using DCDs in the United States, and 15 of 128 (12%) at our institution. Five and 10-year survival for DBDs was 55% and 30% and 59% and 33% for DCDs, respectively. Propensity-matched analysis of 311 DBD/DCD pairs did not demonstrate any difference in survival. On Cox regression, DCD was not associated with impaired survival. Male sex, Karnofsky class greater than 50, double lung transplantation, and transplantation year were predictors of improved survival. Age, creatinine, pulmonary fibrosis, retransplantation, extracorporeal membrane oxygenation, allocation score, and donor age were predictors of worse survival. Primary graft dysfunction at time 0 was worse for recipients of DCDs (p = 0.005) but equivalent at 24, 48, and 72 hours., Conclusions: DCD lung transplants remain underused in the United States. Nevertheless, survival is similar to DBD. Primary graft dysfunction metrics for DCDs are worse than DBDs on intensive care arrival but improved subsequently., (Copyright © 2018 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Background: Existing research demonstrates superior short-term outcomes (length of stay, 1-year survival) after lung transplantation in patients with preoperative functional independence. The aim of this study was to determine whether advantages remain significant in the long-term., Methods: The United Network for Organ Sharing database was queried for adult, first-time, isolated lung transplantation records from January 2005 to December 2015. Stratification was performed based on Karnofsky Performance Status Score (3 groups) and on employment at the time of transplantation (2 groups). Kaplan-Meier and Cox analyses were performed to determine the association between these factors and survival in the long-term., Results: Of 16,497 patients meeting criteria, 1,581 (9.6%) were almost completely independent at the time of transplant vs 5,662 (34.3%) who were disabled (completely reliant on others for activities of daily living). Cox models adjusting for recipient, donor, and transplant factors demonstrated a statistically significant association between disability at the time of transplant and long-term death (hazard ratio, 1.26; 95% confidence interval, 1.14 to 1.40; p < 0.001). There were 15,931 patients with available data on paid employment at the time of transplantation. Multivariable analysis demonstrated a statistically significant association between employment at the time of transplantation and death (hazard ratio, 0.86; 95% confidence interval, 0.75 to 0.91; p < 0.001)., Conclusions: Preoperative functional independence and maintenance of employment are associated with superior long-term outcomes in lung recipients. The results highlight potential benefits of pretransplant functional rehabilitation for patients on the waiting list for lungs., (Copyright © 2018 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Objective: Teaching the next generation operative cardiac surgery while maintaining the highest level of patient care is an ever-increasing challenge given the growing proportion of patients with multiple comorbidities, the loss of more straightforward cases to percutaneous interventions, and the pressure of public reporting. No study to date has compared the outcomes of similar cases performed entirely ("skin-to-skin") by the resident with those performed entirely by the staff to confirm the safety of this practice., Methods: A total of 100 consecutive cardiac cases performed skin-to-skin by the resident (group R) were matched by procedure 1:1 to nonconsecutive cases performed by a single attending surgeon (group A). Patients were excluded from the analysis if there was overlap in any portion of the procedure by the trainee or the attending., Results: Patients in group A were similar to those in group R with respect to age, gender, body mass index, American Society of Anesthesiologists classification, left ventricular ejection fraction, and diabetes mellitus. Mean operative times were longer in group R (4.6 vs 2.7 hours, P < .001), as were cardiopulmonary bypass times (96 vs 50 minutes, P < .001) and aortic crossclamp times (78 vs 39 minutes, P < .001). There were no significant differences in red blood cell transfusions, reexplorations, stroke, length of stay, or wound infections. There were no in-hospital or 30-day deaths., Conclusions: Our data indicate that trainees can be educated in operative surgery under the current paradigm, despite longer operative times, without sacrificing outcome quality. It is reasonable to expect academic programs to continue providing trainees significant experience as primary operating surgeons., (Copyright © 2018 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.)

Background: Kidney transplant patients on tolerance protocols avoid the morbidity associated with the use of conventional chronic immunosuppressive regimens. However, the impact of tolerance versus conventional regimens on the quality of life (QOL) of kidney transplant patients is unknown., Methods: Five patients who achieved long-term immunosuppression-free renal allograft survival after combined kidney and bone marrow transplantation (tolerant group) were compared with thirty-two comparable kidney transplant recipients on conventional immunosuppression (conventional group). QOL was compared with 16 conventional recipients using the Kidney Disease Quality of Life Short Form 36 (KDQOL SF-36) and the Modified Transplant Symptom Occurrence and Symptom Distress Scale (MTSOSD-59R)., Results: Patients in the tolerant group required significantly less treatment after transplant for hypertension and no medications for diabetes ( P < 0.01). There was no incidence of diabetes, dyslipidemia, or malignancies in the tolerant group, while these were observed in 12.5%, 40.6%, and 11.8% of the conventional group, respectively. Tolerant patients experienced better overall health ( P < 0.01) and scored higher on kidney transplant-targeted scales and healthy survey scales than patients in the conventional group according to the KDQOL SF-36 ( P < 0.05). Tolerant patients were less likely to experience depression, dyspnea, excessive appetite/thirst, flatulence, hearing loss, itching, joint pain, lack of energy, muscle cramps, and lack of libido than conventional patients according to the MTSOSD-59R ( P < 0.05)., Conclusion: Kidney transplant recipients who achieved tolerance experience significantly fewer incidences of complications, improved QOL, and fewer comorbid symptoms compared with patients on conventional immunosuppression. These results support the expanded use of tolerance protocols in kidney transplantation.

Regulatory T cells (Treg) play an important role in modulating the immune response and has attracted increasing attention in diverse fields such as cancer treatment, transplantation and autoimmune diseases. CC chemokine receptor 4 (CCR4) is expressed on the majority of Tregs, especially on effector Tregs. Recently we have developed a diphtheria-toxin based anti-human CCR4 immunotoxin for depleting CCR4(+) cells in vivo. In this study, we demonstrated that the anti-human CCR4 immunotoxin bound and depleted monkey CCR4(+) cells in vitro. We also demonstrated that the immunotoxin bound to the CCR4(+)Foxp3(+) monkey Tregs in vitro. In vivo studies performed in two naive cynomolgus monkeys revealed 78-89% CCR4(+)Foxp3(+) Treg depletion in peripheral blood lasting approximately 10 days. In lymph nodes, 89-96% CCR4(+)Foxp3(+) Tregs were depleted. No effect was observed in other cell populations including CD8(+) T cells, other CD4(+) T cells, B cells and NK cells. To our knowledge, this is the first agent that effectively depleted non-human primate (NHP) Tregs. This immunotoxin has potential to deplete effector Tregs for combined cancer treatment., (Copyright © 2015 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.)

Background/aims: There is increasing evidence showing that innate immune responses and inflammatory processes play an important role in the development and progression of diabetic nephropathy (DN). The potential effect of innate immunity in the early stage of DN is still unclear. Toll-Like-Receptor 4 (TLR4) is vigorously involved in the progress of kidney diseases in a sterile environment. The activation of the interleukin 17 (IL-17) pathway produces inflammatory cytokines, appearing in various kidney diseases. Unfortunately the relationship between TLR4 and IL-17 has not been investigated in diabetic nephropathy to date. The aim of this study is to investigate whether mammalian target of rapamycin (mTOR) inhibition may be dependent on TLR4 signaling and the pro-inflammatory factor IL-17 to delay the progression of DN., Methods: Streptozotocin (STZ)-induced diabetic rats were randomly assigned to 3 experimental groups: a diabetic nephropathy group (DN, n = 6); and a diabetic nephropathy treated with rapamycin group (Rapa, n = 6) and a control group (Control, n =6). Body weight, fasting blood sugar, and 24h urine albumin were assessed at week 2, week 4 and week 8. Renal tissues were harvested for H&E, PAS staining, as well as an immunohistochemistry assay for TLR4 and IL-17. TLR4 quantitative expression was measured by Western-Blot analysis and RT-PCR., Results: Our results demonstrated that the expression of both TLR4 and IL-17 were upregulated in early stage DN and reduced by rapamycin. TLR4 and IL-17 both increased and positively related to 24h urinary albumin and kidney/weight ratio. However, neither TLR4 nor IL-17 made a significant difference on fasting blood sugar., Conclusions: Taken together, our results confirm and extend previous studies identifying the significance of the TLR4 and Th17 pathways in development of early stage DN. Furthermore, we suggest this overexpression of TLR4 might be involved in the immunopathogenesis of DN through activation of Th17 cells. Rapamycin may attenuate DN via reduction of the TLR4 signaling pathway and Th17 cells signaling. Although the underlying mechanisms need to be explored, the observed increase of TLR4 and IL-17 during the early stages of DN and their suppression with rapamycin treatment suggest the importance of TLR4 and IL-17 in DN pathophysiology., (© 2016 The Author(s) Published by S. Karger AG, Basel.)

Background: Merkel cell carcinoma (MCC) is a neuroendocrine carcinoma, associated with Merkel cell polyomavirus. MCC admixed with squamous cell carcinoma (SCC) is unassociated with polyomavirus, and is genetically distinct., Objective: We sought to distinguish clinically and dermoscopically between MCC and SCC/MCC., Methods: We compared patient data for SCC/MCC (n = 26) and MCC (n = 20), and reviewed clinical and dermoscopic images (n = 9) of SCC/MCC., Results: Patients with SCC/MCC were older (median 76.5 vs 69 years) and more often male (77% vs 60%), and had more nonmelanoma skin cancer (85% vs 25%), malignant extracutaneous tumors (25% vs 5%), lymphoproliferative disorders (23% vs 10%), and immunodeficient/proinflammatory states (77% vs 35%). In all, 58% of SCC/MCC versus 10% of MCC were clinically diagnosed nonmelanoma skin cancer. Patients with SCC/MCC had more metastases (77% vs 40%), more treatment failures (53% vs 45%), shorter survival (41 vs 54 months), and more death from disease (50% vs 40%). SCC/MCC demonstrated marked scale (7/9), and telangiectasia (1/9). Dermoscopically, small dotted and short linear irregular peripheral vessels and central milky-red areas with large-diameter arborizing vessels were seen., Limitations: The rarity of SCC/MCC limits available data., Conclusions: SCC/MCC is aggressive, arising within elderly patients' chronically ultraviolet-exposed skin, often in the setting of immunosuppression or inflammation. Dermoscopically, polymorphous vessels in lesions suspicious for nonmelanoma skin cancer are suggestive., (Copyright © 2015 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.)

The globalization and externalization of a pharmaceutical company's research and development (R&D) places considerable demands on its underpinning compound management (CM) capability. More robust CM workflows are needed to support higher demands and cross-continent supply chains. The tracking and visibility of compound orders progressing through CM processes has become crucial to ensure prompt and reliable delivery to customers and project timelines worldwide. AstraZeneca at Alderley Park UK has successfully introduced and integrated a visual management system into its CM processes to support the company's global R&D strategy. A simple, low-cost approach has been employed to track solid processing and solubilization orders. This reduced variability and end-to-end cycle times by decreasing waiting time between processing steps. The visual tracking system has been quick to implement, adaptable to change, and able to be owned and run by delivery teams. Introduction of the visual tracking system has resulted in significant improvements in order processing, both in terms of variability and speed. The percentage of orders processed within 24 h rose from 81.5% to 92.5%, and reductions of 50% and 17.5% in the average processing time were seen for solid dispense and solubilization orders, respectively.

MEN2A is a hereditary syndrome characterized by medullary thyroid carcinoma, hyperparathyroidism, and pheochromocytoma. Classically patients with a pheochromocytoma initially present with the triad of paroxysmal headaches, palpitations, and diaphoresis accompanied by marked hypertension. However, although reported as a rare presentation, spontaneous hemorrhage within a pheochromocytoma can present as an abdominal catastrophe. Unrecognized, this transformation can rapidly result in death. We report the only documented case of a thirty eight year old gentleman with MEN2A who presented to a community hospital with hemorrhagic shock and peritonitis secondary to an unrecognized hemorrhagic pheochromocytoma. The clinical course is notable for an inability to localize the source of hemorrhage during an initial damage control laparotomy that stabilized the patient sufficiently to allow emergent transfer to our facility, re-exploration for continued hemorrhage and abdominal compartment syndrome, and ultimately angiographic embolization of the left adrenal artery for control of the bleeding. Following recovery from his critical illness and appropriate medical management for pheochromocytoma, he returned for interval bilateral adrenal gland resection, from which his recovery was unremarkable. Our review of the literature highlights the high mortality associated with the undertaking of an operative intervention in the face of an unrecognized functional pheochromocytoma. This reinforces the need for maintaining a high index of suspicion for pheochromocytoma in similar cases. Our case also demonstrates the need for a mutimodal treatment approach that will often be required in these cases.

Seborrheic keratosis is a common skin lesion that can usually be recognized either clinically or dermoscopically. However, melanomas mimicking seborrheic keratoses, as well as melanomas arising in association with seborrheic keratoses, have been described. We report the case of a patient with a lesion that initially revealed "classic" dermoscopic features of a seborrheic keratosis. However, during follow-up, changes in color developed within the center of the lesion that led the clinician to the correct diagnosis of melanoma. Upon retrospective evaluation of the baseline image of the lesion; the clinician was now able to "see" that which his brain could not appreciate on initial examination and to realize that the lesion had subtle features suspect for melanoma. This case represents a diagnostic pitfall due to errors in perception. Dermatologists should be cognizant of "errors in perception"; we suggest that a final dermoscopic judgment of a seborrheic keratosis be rendered by combining the gestalt diagnosis of the overall pattern, with deliberate dermoscopic analysis of all quadrants of the lesion.

Background: Trichoepitheliomas (TE) are benign neoplasms of follicular differentiation. Solitary lesions are often confused with basal cell carcinoma (BCC). Reflectance confocal microscopy (RCM) and dermoscopy are imaging tools for in vivo, noninvasive evaluation of skin lesions. To date, there has been no description of their findings in the evaluation of TE., Objective: Our aim is to describe the dermoscopic and RCM findings of histopathologically confirmed TE., Methods: Four TE were evaluated, 2 each of the desmoplastic and nondesmoplastic variants. RCM was performed on 1 of the desmoplastic and both of the nondesmoplastic lesions., Results: Dermoscopically, all of the lesions showed arborizing telangiectasias. The desmoplastic lesions also had an ivory-white background throughout. RCM showed oval, darker-appearing tumor islands that contained brightly refractile material, consistent with keratin horn cysts at the center, as well as parallel bundles of highly refractile dermal collagen surrounding the tumor islands., Conclusion: The ivory-white background throughout the lesion seen on dermoscopy may be helpful in distinguishing desmoplastic TE from BCC. The RCM findings in TE of keratin-filled cysts in tumor islands and attachment of the tumor to follicular structures have not been previously observed in BCC, and thus may also be diagnostically helpful. Further study is necessary for validation of these findings., (2007 S. Karger AG, Basel)