OBJECTIVES Right ventricular (RV) failure after left ventricular assist device (LVAD) implantation continues to be a morbid complication. In this study, we hypothesized that a less invasive approach to implantation would preserve RV function relative to a conventional sternotomy (CS) approach. METHODS All patients (2013–2017) who underwent LVAD implantation were reviewed. Patients were stratified by surgical approach: less invasive left thoracotomy with hemi-sternotomy (LTHS) and CS. The primary outcome was severe RV failure. RESULTS Eighty-three patients (LTHS: 37, CS: 46) were identified. The median Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) score was significantly worse in the LTHS compared to the CS cohort, and there was a trend towards higher RV failure scores and HeartMate II mortality scores. Preoperative RV dysfunction, in pulmonary artery pulsatility index and RV stroke work index were similar between the 2 groups. Though operative time did not significantly differ between the 2 groups, cardiopulmonary bypass time was significantly shorter in the LTHS group (61 vs 95 min, P < 0.001). The incidence of postoperative severe RV failure was significantly reduced in the LTHS group (16% vs 39%, P = 0.030), along with the need for temporary right ventricular assist device (3% vs 26%, P = 0.005). Improvement in RV function, along with a change in pulmonary artery pulsatility index, was significantly greater in the LTHS cohort. There was a trend towards improved Kaplan–Meier 1-year survival in the LTHS cohort (91% vs 56%, P = 0.056). CONCLUSIONS In this cohort, less invasive LVAD implantation appears to be associated with reduced postoperative RV failure, and equivalent or improved survival compared to conventional LVAD implantation.

A combination of genetic manipulations of donor organs and target‐specific immunosuppression is instrumental in achieving long‐term cardiac xenograft survival. Recently, results from our preclinical pig‐to‐baboon heterotopic cardiac xenotransplantation model suggest that a three‐pronged approach is successful in extending xenograft survival: (a) α‐1,3‐galactosyl transferase (Gal) gene knockout in donor pigs (GTKO) to prevent Gal‐specific antibody‐mediated rejection; (b) transgenic expression of human complement regulatory proteins (hCRP; hCD46) and human thromboregulatory protein thrombomodulin (hTBM) to avoid complement activation and coagulation dysregulation; and (c) effective induction and maintenance of immunomodulation, particularly through co‐stimulation blockade of CD40‐CD40L pathways with anti‐CD40 (2C10R4) monoclonal antibody (mAb). Using this combination of manipulations, we reported significant improvement in cardiac xenograft survival. In this study, we are reporting the survival of cardiac xenotransplantation recipients (n = 3) receiving xenografts from pigs without the expression of hTBM (GTKO.CD46). We observed that all grafts underwent rejection at an early time point (median 70 days) despite utilization of our previously reported successful immunosuppression regimen and effective control of non‐Gal antibody response. These results support our hypothesis that transgenic expression of human thrombomodulin in donor pigs confers an independent protective effect for xenograft survival in the setting of a co‐stimulation blockade‐based immunomodulatory regimen.

We identified a sequence embedded in the U3/R region of HIV-1 RNA that is highly complementary to human tRNA3Lys. The free energy of annealing to tRNA3Lys is significantly lower for this sequence and the primer-binding site than for other similar length viral sequences. The only interruption in complementarity is a 29-nucleotide segment inserted where a tRNA intron would be expected. The insert contains the TATA box for viral RNA transcription. The embedded sequence includes a nine-nucleotide segment previously reported to aid minus strand transfer by binding the primer tRNA3Lys. Reconstituting transfer in vitro, we show that including segments from the embedded sequence in the acceptor template, beyond the nine nucleotides, further increases transfer efficiency. We propose that a tRNA3Lys gene was incorporated during HIV-1 evolution and retained largely intact because of its roles in transcription and strand transfer.

Timing of tracheostomy placement for patients with respiratory failure requiring venovenous extracorporeal membrane oxygenation support is variable and continues to depend on surgeon preference. We retrospectively reviewed all consecutive adult patients supported with peripheral venovenous extracorporeal membrane oxygenation for acute respiratory distress syndrome at a single institution with the hypothesis that early tracheostomy (within 7 days of extracorporeal membrane oxygenation initiation) decreases the duration of extracorporeal membrane oxygenation support. The primary endpoint was duration of extracorporeal membrane oxygenation support. Secondary endpoints included mortality, overall and intensive care unit length of stay, duration of mechanical ventilation, and time from extracorporeal membrane oxygenation initiation to liberation from ventilator, intensive care unit discharge, and hospital discharge. Overall and extracorporeal membrane oxygenation–associated hospital costs were compared. A total of 50 patients were identified for inclusion (early n = 21; late n = 29). Baseline characteristics including indices of disease severity were similar between groups. Duration of extracorporeal membrane oxygenation support was significantly shorter in the early tracheostomy group (12 vs. 21 days; p = 0.005). Median extracorporeal membrane oxygenation–related costs were significantly decreased in the early tracheostomy group ($3,624 vs. $5,603, p = 0.03). Early tracheostomy placement is associated with decreased time on extracorporeal membrane oxygenation support and reduced extracorporeal membrane oxygenation–related costs in this cohort. Validation in a prospective cohort or a clinical trial is indicated.

Background.-Peri-operative cardiac xenograft dysfunction (PCXD) was described by McGregor et al. to be a major barrier to the translation of heterotopic cardiac xenotransplantaton into the orthotopic position. It is characterized by graft dysfunction in the absence of rejection within 24-48 hours of transplantation. We describe our experience with PCXD at a single program.Methods.-Orthotopic transplantation of genetically engineered pig hearts was performed in 6 healthy baboons. The immunosuppression regimen included induction by anti-CD20 mAb, Thymoglobulin, cobra venom factor and anti-CD40 mAb and maintenance with anti-CD40 mAb, MMF and tapering doses of steroids. Telemetry was used to asses graft function. Extracorporeal membrane oxygenation was used to support one recipient. A full human clinical transplant team was involved in these experiments and the procedure was performed by skilled transplant surgeons.Results.-A maximal survival of 40 hours was achieved in these experiments. The surgical procedures were uneventful and all hearts were weaned from cardiopulmonary bypass (CPB) without issue. Support with inotropes and vasopressors was generally required after separation from CPB. The cardiac xenografts performed well immediately, but within the first several hours required increasing support and ultimately suffered arrest despite maximal interventions. All hearts were explanted immediately; histology showed no signs of rejection.

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Lung ischemia-reperfusion injury (LIRI) and primary graft dysfunction are leading causes of morbidity and mortality among lung transplant recipients. Although extensive research endeavors have been undertaken, few preventative and therapeutic treatments have emerged for clinical use. Novel strategies are still needed to improve outcomes after lung transplantation. In this review, we discuss the underlying mechanisms of transplanted LIRI, potential modifiable targets, current practices, and areas of ongoing investigation to reduce LIRI and primary graft dysfunction in lung transplant recipients.

Supplementary data are available at Bioinformatics online.