Analysis of sex-based differences in clinical and molecular responses to ischemia reperfusion after lung transplantation.

BACKGROUND: Sex and hormones influence immune responses to ischemia reperfusion (IR) and could, therefore, cause sex-related differences in lung transplantation (LTx) outcomes. We compared men's and women's clinical and molecular responses to post-LTx IR. METHODS: In 203 LTx patients, we used the 2016 International Society for Heart and Lung Transplantation guidelines to score primary graft dysfunction (PGD). In a subgroup of 40 patients with blood samples collected before LTx (T0) and 6, 24, 48 (T48), and 72 h (T72) after lung reperfusion, molecular response to IR was examined through serial analysis of circulating cytokine expression. RESULTS: After adjustment, women had less grade 3 PGD than men at T48, but not at T72. PGD grade decreased from T0 to T72 more often in women than men. The evolution of PGD (the difference in mean PGD between T72 and T0) was greater in men. However, the evolution of IL-2, IL-7, IL-17a, and basic fibroblast growth factor levels was more often sustained throughout the 72 h in women. In the full cohort, we noted no sex differences in secondary clinical outcomes, but women had significantly lower peak lactate levels than men across the 72 h. CONCLUSIONS: Men and women differ in the evolution of PGD and cytokine secretion after LTx: Women have a more sustained proinflammatory response than men despite a greater reduction in PGD over time. This interaction between cytokine and PGD responses warrants investigation. Additionally, there may be important sex-related differences that could be used to tailor treatment during or after transplantation.

Incidence of primary graft dysfunction is higher according to the new ISHLT 2016 guidelines and correlates with clinical and molecular risk factors.

BACKGROUND: Primary graft dysfunction (PGD) is the most important determinant of morbidity and mortality after lung transplantation, but its definition has evolved over the past decade. The implications of this refinement in clinical definition have not been evaluated. In this single-center study, we compared PGD incidence, risk factors, and outcomes using the 2005 and the updated-2016 International Society of Heart and Lung Transplantation guidelines for PGD grading in lung transplant patients. METHODS: In this retrospective study, we extracted data from the medical records of 127 patients who underwent lung transplantation between 1/1/2016-12/31/2018. PGD was defined as PGD3 present at 48 and/or 72 hours post-reperfusion. We used the 2005 and the updated 2016 guidelines to assess clinical risk factors, outcomes, and baseline biomarkers for PGD. RESULTS: On the basis of the 2016 and 2005 guidelines, we identified PGD in 37% and 26% of patients, respectively. PGD was significantly associated with extracorporeal life support, large body mass index, and restrictive lung disease using the 2016 but not the 2005 guidelines. Based on the 2016 guidelines, pretransplant levels of several biomarkers were associated with PGD; using the 2005 guidelines, only increased interleukin-2 levels were significantly associated with PGD. No preoperative biomarkers were associated with PGD using either guidelines after adjusting for clinical variables. Postoperative morbidity and 1-year mortality were similar regardless of guidelines used. CONCLUSIONS: Our findings suggest that refinements in the PGD scoring system have improved the detection of graft injury and associated risk factors without changing its ability to predict postoperative morbidity and mortality.

Light-controlled release of nitric oxide from solid polymer composite materials using visible and near infra-red light.

Photochemical Nitric oxide releasing composite materials (Photo-NORMs) were prepared using biocompatible polymers and the photochemical nitric oxide donor complex (CrONO). We have demonstrated nitric oxide (NO) release from the solid composites for extended (>30 hours) and controlled (20-100 pmoles s(-1)) durations after visible light irradiation. Quantitation of the efficiency of NO release from the composites shows that polymer gas permeability most dramatically affects the overall efficiency (QY) of photochemical NO release, where polymers with higher gas permeability have a higher QY of nitric oxide release. Composites were also prepared with ß-phase lanthanide-doped NaYF4 upconverting nanoparticles (UCNPs). Controlled Nitric oxide release was achieved via near infrared (NIR) irradiation. A prototype LED device shows proof-of-concept that such photoresponsive NO-releasing composites could be applied to implantable systems, where the amount of NO released is modulated by changing irradiation time and light intensity. This research provides the guidelines necessary to move towards device fabrication and testing in actual tissue to evaluate the photo-NORMS as a reliable option for nitric oxide release in vivo.