Roland Brown

Prolonged EVLP Using OCS Lung: Cellular and Acellular Perfusates.

Background We report the ability to extend lung preservation up to 24 hours (24H) by using autologous whole donor blood circulating within an ex vivo lung perfusion (EVLP) system. This approach facilitates donor lung reconditioning in a model of extended normothermic EVLP. We analyzed comparative responses to cellular and acellular perfusates to identify these benefits. Methods Twelve pairs of swine lungs were retrieved after cardiac arrest and studied for 24H on the Organ Care System (OCS) Lung EVLP platform. Three groups (n = 4 each) were differentiated by perfusate: (1) isolated red blood cells (RBCs) (current clinical standard for OCS); (2) whole blood (WB); and (3) acellular buffered dextran-albumin solution (analogous to STEEN solution). Results Only the RBC and WB groups met clinical standards for transplantation at 8 hours; our primary analysis at 24H focused on perfusion with WB versus RBC. The WB perfusate was superior (vs RBC) for maintaining stability of all monitored parameters, including the following mean 24H measures: pulmonary artery pressure (6.8 vs 9.0 mm Hg), reservoir volume replacement (85 vs 1607 mL), and PaO2:FiO2 ratio (541 vs 223). Acellular perfusion was limited to 6 hours on the OCS system due to prohibitively high vascular resistance, edema, and worsening compliance. Conclusions The use of an autologous whole donor blood perfusate allowed 24H of preservation without functional deterioration and was superior to both RBC and buffered dextran-albumin solution for extended lung preservation in a swine model using OCS Lung. This finding represents a potentially significant advance in donor lung preservation and reconditioning.

An Experimental Study of the Recovery of Injured Porcine Lungs with Prolonged Normothermic Cellular Ex Vivo Lung Perfusion Following Donation after Circulatory Death

Donation after circulatory death (DCD) is an underused source of donor lungs. Normothermic cellular ex vivo lung perfusion (EVLP) is effective in preserving standard donor lungs but may also be useful in the preservation and assessment of DCD lungs. Using a model of DCD and prolonged EVLP, the effects of donor warm ischemia and postmortem ventilation on graft recovery were evaluated. Adult male swine underwent general anesthesia and heparinization. In the control group (n = 4), cardioplegic arrest was induced and the lungs were procured immediately. In the four treatment groups, a period of agonal hypoxia was followed by either 1 h of warm ischemia with (n = 4) or without (n = 4) ventilation or 2 h of warm ischemia with (n = 4) or without (n = 4) ventilation. All lungs were studied on an EVLP platform for 24 h. Hemodynamic measures, compliance, and oxygenation on EVLP were worse in all DCD lungs compared with controls. Hemodynamics and compliance normalized in all lungs after 24 h of EVLP, but DCD lungs demonstrated impaired oxygenation. Normothermic cellular EVLP is effective in preserving and monitoring of DCD lungs. Early donor postmortem ventilation and timely procurement lead to improved graft function.

Laryngeal Mask Airway for Surfactant Administration in Neonates: A Randomized, Controlled Trial

Objective To determine if preterm infants with moderate respiratory distress syndrome on continuous positive airway pressure (CPAP) who received surfactant via a laryngeal mask airway (LMA) would have a decreased rate of intubation and mechanical ventilation compared with those on CPAP who did not receive surfactant. Study design In this prospective, multicenter, randomized controlled trial, 103 premature infants 280/7‐356/7 weeks gestation, ≥1250 g and ≤36 hours old on CPAP requiring fraction of inspired oxygen 0.30‐0.40 were assigned to receive surfactant administered through an LMA then placed back on CPAP (LMA group) or maintained on CPAP with no surfactant administered (control group). The primary outcome was treatment failure necessitating intubation and mechanical ventilation in the first 7 days of life. Results Surfactant administration through an LMA (n = 50) significantly decreased the rate of intubation and mechanical ventilation compared with controls (n = 53): 38% vs 64%, respectively, OR 0.30 (95% CI 0.13, 0.70), P = .006, number needed to treat: 4). There were no serious adverse events associated with placement of the LMA or surfactant administration. Conclusions In premature neonates with moderate respiratory distress syndrome, surfactant administered through an LMA decreased the rate of intubation and mechanical ventilation. This intervention may have significant impact on clinical care in both high and low resource settings. Trial registration ClinicalTrials.gov: NCT01116921.

Gender differences in long-term survival post-transplant: A single-institution analysis in the lung allocation score era

The purpose of this study was to clarify the significance of recipient gender status on lung transplant outcomes in a large single‐institution experience spanning three decades, we analyzed data from all lung transplants performed in our institution since 1986. Kaplan‐Meier curves and Cox proportional hazard models were used to evaluate the effect of recipient characteristics on survival and BOS score ≥1‐free survival. Logistic regression analysis was used to explore the association of gender with short‐term graft function. About 876 lung transplants were performed between 1986 and 2016. Kaplan‐Meier survival estimates at 5 years post‐transplant for females vs males in the LAS era were 71% vs 58%. In the LAS era, females showed greater unadjusted BOS≥1‐free survival than males (35% vs 25%, P=.02) over 5 years. Female gender was the only factor in the LAS era significantly associated with improved adjusted 5‐year survival [HR 0.56 (95% CI 0.33, 0.95) P=.03]. Conversely, in the pre‐LAS era female gender was not associated with improved survival. Female recipients showed significantly improved survival over 5 years compared to males in the LAS era. A prospective analysis of biologic and immunologic differences is warranted.

Lung transplant after prolonged ex vivo lung perfusion: predictors of allograft function in swine

Portable normothermic EVLP has been evaluated in clinical trials using standard and extended‐criteria donor lungs. We describe a swine model of lung transplant following donation after circulatory death using prolonged normothermic EVLP to assess the relationship between EVLP data and acute lung allograft function. Adult swine were anesthetized and heparinized. In the control group (n = 4), lungs were procured, flushed, and transplanted. Treatment swine underwent either standard procurement (n = 3) or agonal hypoxia followed by 1 (n = 4) or 2 hours (H) (n = 4) of ventilated warm ischemia. Lungs were preserved for 24H using normothermic blood‐based EVLP then transplanted. Recipients were monitored for 4 H. After 24H of preservation, mean pulmonary artery pressure (mPAP), pulmonary vascular resistance (PVR), and dynamic compliance (Cdyn) were improved in all EVLP groups. After transplant, EVLP groups showed similar allograft oxygenation. EVLP PVR, mPAP, and lung block weights had significant negative correlations with post‐transplant allograft oxygenation. EVLP P:F ratio did not correlate with acute post‐transplant allograft function until 24H of preservation. Data measured in the first 8H of EVLP were sufficient for predicting acute post‐transplant allograft function. This study provides a benchmark and platform for evaluation of therapies for donor‐related allograft injury in injured lungs treated with prolonged normothermic EVLP.

Variations in 24-Hour BP Profiles in Cohorts of Patients with Kidney Disease around the World: The I-DARE Study

BACKGROUND AND OBJECTIVES Ambulatory BP is increasingly recognized as a better measure of the risk for adverse outcomes related to hypertension, an important comorbidity in patients with CKD. Varying definitions of white-coat and masked hypertension have made it difficult to evaluate differences in prevalence of these BP patterns across CKD cohorts. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS The International Database of Ambulatory BP in Renal Patients collaborative group established a large database of demographic, clinical, and ambulatory BP data from patients with CKD from cohorts in Italy, Spain, the Chronic Renal Insufficiency Cohort (CRIC) and the African American Study of Kidney Disease and Hypertension Cohort Study (AASK) in the United States, and the CKD Japan Cohort (CKD-JAC). Participants (n=7518) with CKD were included in the present analyses. Cutoffs for defining controlled BP were 140/90 mm Hg for clinic and 130/80 mm Hg for 24-hour ambulatory BP. RESULTS Among those with controlled clinic BP, compared with CKD-JAC, AASK participants were more likely to have masked hypertension (prevalence ratio [PR], 1.21; 95% confidence interval [95% CI], 1.04 to 1.41) whereas CRIC (PR, 0.82; 0.72 to 0.94), Italian (PR, 0.73; 0.56 to 0.95), and Spanish participants (PR, 0.75; 0.64 to 0.88) were less likely. Among those with elevated clinic BP, AASK participants were more likely to have sustained hypertension (PR, 1.22; 95% CI, 1.13 to 1.32) whereas Italian (PR, 0.78; 0.70 to 0.87) and Spanish participants (PR, 0.89; 0.82 to 0.96) were less likely, although CRIC participants had similar prevalence as CKD-JAC. Prevalence of masked and sustained hypertension was elevated in males, patients with diabetes, participants on four or more antihypertensives, and those with moderate-to-severe proteinuria. CONCLUSIONS In a large, multinational database, the prevalence of masked and sustained hypertension varied across cohorts independent of important comorbidities.

Determination of bilateral symmetry of carotid artery structure and function in children and adolescents

We compared the symmetry of carotid arteries in youth with high-resolution ultrasound. Participants (n=230 (121 females),13.8 ± 2.9 years old) were assessed for: intima media thickness (cIMT), lumen diameter (cLD), incremental elastic modulus (cIEM), diameter compliance (cDC), cross-sectional compliance (cCSC), diameter distensibility (cDD), and cross-sectional distensibility (cCSD). No significant differences (P >0.05 all) were found for cIMT (0.49 ± 0.09 mm vs. 0.49 ± 0.08 mm), cIEM (1095 ± 382 mmHg vs. 1116 ± 346mmHg), cDC (0.01 ± 0.0 mm/mmHg vs. 0.01 ± 0.0 mm/mmHg), cCSC (0.01 ± 0.001/mmHg vs. 0.01 ± 0.001/mmHg), cDD (14.0 ± 3.16% vs. 13.7 ± 3.18%), and cCSD (30.1 ± 7.37% vs. 29.4 ± 7.36%). Significant differences were found for cLD (6.06 ± 0.62 mm vs. 6.33 ± 0.64 mm, P <0.001). These data suggest that these values may be used interchangeably if one side is inaccessible.

Removal notice to (617) – Candida Colonization Is Associated with Improved Survival After Lung Transplant J Heart Lung Transplant 36 (2017) S238

J.S. Green, R. Brown, T. Umeda, K. Rudser, S. Elde, J.M. Roberts, M.I. Hertz, G. Loor, J.H. Young, and R. Tomic, From the Medicine, Infectious Diseases, University of Minnesota, Minneapolis, MN; PUBHL Biostatistics Division, University of Minnesota, Minneapolis, MN; Medicine, PAAC Medicine, University of Minnesota, Minneapolis, MN been removed at the request of the Editor-in-Chief and Author. Following publication of the abstract the authors realized that there were a conglomerate of assumptions and discrepancies in the data. The published abstract has therefore been removed.