Background Heart transplantation (HTx) from brainstem dead (BSD) donors is the gold-standard ther... more Background Heart transplantation (HTx) from brainstem dead (BSD) donors is the gold-standard therapy for severe/end-stage cardiac disease, but is limited by a global donor heart shortage. Consequently, innovative solutions to increase donor heart availability and utilisation are rapidly expanding. Clinically relevant preclinical models are essential for evaluating interventions for human translation, yet few exist that accurately mimic all key HTx components, incorporating injuries beginning in the donor, through to the recipient. To enable future assessment of novel perfusion technologies in our research program, we thus aimed to develop a clinically relevant sheep model of HTx following 24 h of donor BSD. Methods BSD donors (vs. sham neurological injury, 4/group) were hemodynamically supported and monitored for 24 h, followed by heart preservation with cold static storage. Bicaval orthotopic HTx was performed in matched recipients, who were weaned from cardiopulmonary bypass (CPB)...
Background A lung transplant is the last resort treatment for many patients with advanced lung di... more Background A lung transplant is the last resort treatment for many patients with advanced lung disease. The majority of donated lungs come from donors following brain death (BD). The endothelin axis is upregulated in the blood and lung of the donor after BD resulting in systemic inflammation, lung damage and poor lung graft outcomes in the recipient. Tezosentan (endothelin receptor blocker) improves the pulmonary haemodynamic profile; however, it induces adverse effects on other organs at high doses. Application of ex vivo lung perfusion (EVLP) allows the development of organ-specific hormone resuscitation, to maximise and optimise the donor pool. Therefore, we investigate whether the combination of EVLP and tezosentan administration could improve the quality of donor lungs in a clinically relevant 6-h ovine model of brain stem death (BSD). Methods After 6 h of BSD, lungs obtained from 12 sheep were divided into two groups, control and tezosentan-treated group, and cannulated for EV...
Background. Access to lung transplantation (LTx) and rates of waiting list and posttransplant mor... more Background. Access to lung transplantation (LTx) and rates of waiting list and posttransplant mortality for patients with interstitial lung disease (ILD) remain problematic. We evaluated the outcomes of ILD patients listed for LTx at our institution. Methods. Between 2012 and 2018, adult patients with ILD were listed and transplanted from a donor-pool that included extended criteria and donation after circulatory-determined death donors. Patients were categorized as experiencing 1 of 4 competing events: transplant, waitlist death, delisting, or alive on waitlist. Multivariable competing risk regression analysis was performed to determine predictors of waitlist death/delisting. Posttransplant survival was analyzed using Kaplan-Meier methods. Results. Among 187 patients listed, 82% (153 of 187) underwent LTx (median time-to-transplant, 2.0 mo), whereas 16% (30 of 187) died or were delisted (median time-to-event, 1.6 mo). At 90 d, 6 mo, and 12 mo after listing, 51%, 63%, and 78% of pat...
Surgical pulmonary embolectomy (SPE) is a viable treatment approach for subsets of patients with ... more Surgical pulmonary embolectomy (SPE) is a viable treatment approach for subsets of patients with acute pulmonary embolism. However, outcomes data are limited. We sought to characterize mortality and safety outcomes for this population. Studies reporting inhospital mortality for patients undergoing SPE for acute pulmonary embolism were included. In 56 eligible studies, we found 1,579 patients who underwent 1,590 SPE operations. The pooled inhospital all-cause mortality rate was 26.3% (95% confidence interval: 22.5% to 30.5%). Surgical site complications occurred in 7.0% of operations (95% confidence interval: 4.9% to 9.8%). More investigation is required to define the patient population that would benefit the most from SPE.
Ventricular assist device (VAD)-specific infections, in particular, driveline infections, are a c... more Ventricular assist device (VAD)-specific infections, in particular, driveline infections, are a concerning complication of VAD implantation that often results in significant morbidity and even mortality. The presence of a percutaneous driveline at the skin exit-site and in the subcutaneous tunnel allows biofilm formation and migration by many bacterial and fungal pathogens. Biofilm formation is an important microbial strategy, providing a shield against antimicrobial treatment and human immune responses; biofilm migration facilitates the extension of infection to deeper tissues such as the pump pocket and the bloodstream. Despite the introduction of multiple preventative strategies, driveline infections still occur with a high prevalence of ~10–20% per year and their treatment outcomes are frequently unsatisfactory. Clinical diagnosis, prevention and management of driveline infections are being targeted to specific microbial pathogens grown as biofilms at the driveline exit-site or ...
In an era of increasing ex vivo lung perfusion (EVLP) use, it remains important to describe what ... more In an era of increasing ex vivo lung perfusion (EVLP) use, it remains important to describe what outcomes can be achieved without EVLP, by taking an aggressive approach to donor use to maximize lung transplantation. Data for all lung transplant donor referrals to the Alfred Hospital in Melbourne, Australia were collected for 2012 to 2013. Donor variables were analyzed and calculated into a previously validated lung donor score. Lung transplant recipient outcome data included the following: primary graft dysfunction; duration of mechanical ventilation; need for cardiopulmonary bypass extracorporeal membrane oxygenation; intensive care and hospital length of stay; 30-day, 1-year, and 3- to 4-year survival rates; rates of acute rejection and chronic lung allograft dysfunction; and peak and 12-month lung function (forced expiratory volume in 1 second). Of the 318 lung donor offers, 129 resulted in successful lung transplantation, with an overall donor use rate of 41%. There was no corre...
Background Heart transplantation (HTx) from brainstem dead (BSD) donors is the gold-standard ther... more Background Heart transplantation (HTx) from brainstem dead (BSD) donors is the gold-standard therapy for severe/end-stage cardiac disease, but is limited by a global donor heart shortage. Consequently, innovative solutions to increase donor heart availability and utilisation are rapidly expanding. Clinically relevant preclinical models are essential for evaluating interventions for human translation, yet few exist that accurately mimic all key HTx components, incorporating injuries beginning in the donor, through to the recipient. To enable future assessment of novel perfusion technologies in our research program, we thus aimed to develop a clinically relevant sheep model of HTx following 24 h of donor BSD. Methods BSD donors (vs. sham neurological injury, 4/group) were hemodynamically supported and monitored for 24 h, followed by heart preservation with cold static storage. Bicaval orthotopic HTx was performed in matched recipients, who were weaned from cardiopulmonary bypass (CPB)...
Background A lung transplant is the last resort treatment for many patients with advanced lung di... more Background A lung transplant is the last resort treatment for many patients with advanced lung disease. The majority of donated lungs come from donors following brain death (BD). The endothelin axis is upregulated in the blood and lung of the donor after BD resulting in systemic inflammation, lung damage and poor lung graft outcomes in the recipient. Tezosentan (endothelin receptor blocker) improves the pulmonary haemodynamic profile; however, it induces adverse effects on other organs at high doses. Application of ex vivo lung perfusion (EVLP) allows the development of organ-specific hormone resuscitation, to maximise and optimise the donor pool. Therefore, we investigate whether the combination of EVLP and tezosentan administration could improve the quality of donor lungs in a clinically relevant 6-h ovine model of brain stem death (BSD). Methods After 6 h of BSD, lungs obtained from 12 sheep were divided into two groups, control and tezosentan-treated group, and cannulated for EV...
Background. Access to lung transplantation (LTx) and rates of waiting list and posttransplant mor... more Background. Access to lung transplantation (LTx) and rates of waiting list and posttransplant mortality for patients with interstitial lung disease (ILD) remain problematic. We evaluated the outcomes of ILD patients listed for LTx at our institution. Methods. Between 2012 and 2018, adult patients with ILD were listed and transplanted from a donor-pool that included extended criteria and donation after circulatory-determined death donors. Patients were categorized as experiencing 1 of 4 competing events: transplant, waitlist death, delisting, or alive on waitlist. Multivariable competing risk regression analysis was performed to determine predictors of waitlist death/delisting. Posttransplant survival was analyzed using Kaplan-Meier methods. Results. Among 187 patients listed, 82% (153 of 187) underwent LTx (median time-to-transplant, 2.0 mo), whereas 16% (30 of 187) died or were delisted (median time-to-event, 1.6 mo). At 90 d, 6 mo, and 12 mo after listing, 51%, 63%, and 78% of pat...
Surgical pulmonary embolectomy (SPE) is a viable treatment approach for subsets of patients with ... more Surgical pulmonary embolectomy (SPE) is a viable treatment approach for subsets of patients with acute pulmonary embolism. However, outcomes data are limited. We sought to characterize mortality and safety outcomes for this population. Studies reporting inhospital mortality for patients undergoing SPE for acute pulmonary embolism were included. In 56 eligible studies, we found 1,579 patients who underwent 1,590 SPE operations. The pooled inhospital all-cause mortality rate was 26.3% (95% confidence interval: 22.5% to 30.5%). Surgical site complications occurred in 7.0% of operations (95% confidence interval: 4.9% to 9.8%). More investigation is required to define the patient population that would benefit the most from SPE.
Ventricular assist device (VAD)-specific infections, in particular, driveline infections, are a c... more Ventricular assist device (VAD)-specific infections, in particular, driveline infections, are a concerning complication of VAD implantation that often results in significant morbidity and even mortality. The presence of a percutaneous driveline at the skin exit-site and in the subcutaneous tunnel allows biofilm formation and migration by many bacterial and fungal pathogens. Biofilm formation is an important microbial strategy, providing a shield against antimicrobial treatment and human immune responses; biofilm migration facilitates the extension of infection to deeper tissues such as the pump pocket and the bloodstream. Despite the introduction of multiple preventative strategies, driveline infections still occur with a high prevalence of ~10–20% per year and their treatment outcomes are frequently unsatisfactory. Clinical diagnosis, prevention and management of driveline infections are being targeted to specific microbial pathogens grown as biofilms at the driveline exit-site or ...
In an era of increasing ex vivo lung perfusion (EVLP) use, it remains important to describe what ... more In an era of increasing ex vivo lung perfusion (EVLP) use, it remains important to describe what outcomes can be achieved without EVLP, by taking an aggressive approach to donor use to maximize lung transplantation. Data for all lung transplant donor referrals to the Alfred Hospital in Melbourne, Australia were collected for 2012 to 2013. Donor variables were analyzed and calculated into a previously validated lung donor score. Lung transplant recipient outcome data included the following: primary graft dysfunction; duration of mechanical ventilation; need for cardiopulmonary bypass extracorporeal membrane oxygenation; intensive care and hospital length of stay; 30-day, 1-year, and 3- to 4-year survival rates; rates of acute rejection and chronic lung allograft dysfunction; and peak and 12-month lung function (forced expiratory volume in 1 second). Of the 318 lung donor offers, 129 resulted in successful lung transplantation, with an overall donor use rate of 41%. There was no corre...
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Papers by David McGiffin