Julian Gooi

Cadaveric Lobar Lung Transplantation: Technical Aspects

BACKGROUND The use of lobar transplantation and other size reduction techniques has allowed larger donor lungs to be utilized for smaller recipients who tend to have longer waiting times for transplantation. However, despite these advantages, the techniques have not been widely adopted. We outline the surgical and sizing issues associated with this technique. METHODS A retrospective review of 23 consecutive patients who received lung transplantation with anatomic lobar reduction was performed, focusing on surgical technique and outcomes. RESULTS All 23 patients received an anatomic lobar reduction of between 1 and 3 lobes. Survival analysis showed no difference between the lobar reduction cohort and the other historically comparable lung transplant patients from our institution (p=0.115). Percent predicted forced vital capacity and forced expiratory volume in 1 second at 3 months correlated with transplanted donor to recipient total lung capacity ratio, confirming the importance of correct sizing. CONCLUSIONS Anatomic lobar reduction in lung transplantation is a safe and effective means of transplanting pediatric and small adult recipients, and urgently listed patients.

Sustained function of genetically modified porcine lungs in an ex vivo model of pulmonary xenotransplantation

BACKGROUND Xenotransplantation could provide a solution to the donor shortage that is currently the major barrier to solid-organ transplantation. The ability to breed pigs with multiple genetic modifications provides a unique opportunity to explore the immunologic challenges of pulmonary xenotransplantation. METHODS Explanted lungs from wild-type and 3 groups of genetically modified pigs were studied: (i) α1,3-galactosyltransferase gene knockout (GTKO); (ii) GTKO pigs expressing the human complementary regulatory proteins CD55 and CD59 (GTKO/CD55-59); and (iii) GTKO pigs expressing both CD55-59 and CD39 (GTKO/CD55-59/CD39). The physiologic, immunologic and histologic properties of porcine lungs were evaluated on an ex vivo rig after perfusion with human blood. RESULTS Lungs from genetically modified pigs demonstrated stable pulmonary vascular resistance and better oxygenation of the perfusate, and survived longer than wild-type lungs. Physiologic function was inversely correlated with the degree of platelet sequestration into the xenograft. Despite superior physiologic profiles, lungs from genetically modified pigs still showed evidence of intravascular thrombosis and coagulopathy after perfusion with human blood. CONCLUSIONS The ability to breed pigs with multiple genetic modifications, and to evaluate lung physiology and histology in real-time on an ex vivo rig, represent significant advances toward better understanding the challenges inherent to pulmonary xenotransplantation.

Carbon dioxide insufflation in open-chamber cardiac surgery: A double-blind, randomized clinical trial of neurocognitive effects

OBJECTIVE The aims of this study were first to analyze neurocognitive outcomes of patients after open-chamber cardiac surgery to determine whether carbon dioxide pericardial insufflation reduces incidence of neurocognitive decline (primary end point) as measured 6 weeks postoperatively and second to assess the utility of carbon dioxide insufflation in cardiac chamber deairing as assessed by transesophageal echocardiography. METHODS A multicenter, prospective, double-blind, randomized, controlled trial compared neurocognitive outcomes in patients undergoing open-chamber (left-sided) cardiac surgery who were assigned carbon dioxide insufflation or placebo (control group) in addition to standardized mechanical deairing maneuvers. RESULTS One hundred twenty-five patients underwent surgery and were randomly allocated. Neurocognitive testing showed no clinically significant differences in z scores between preoperative and postoperative testing. Linear regression was used to identify factors associated with neurocognitive decline. Factors most strongly associated with neurocognitive decline were hypercholesterolemia, aortic atheroma grade, and coronary artery disease. There was significantly more intracardiac gas noted on intraoperative transesophageal echocardiography in all cardiac chambers (left atrium, left ventricle, and aorta) at all measured times (after crossclamp removal, during weaning from cardiopulmonary bypass, and at declaration of adequate deairing by the anesthetist) in the control group than in the carbon dioxide group (P < .04). Deairing time was also significantly longer in the control group (12 minutes [interquartile range, 9-18] versus 9 minutes [interquartile range, 7-14 minutes]; P = .002). CONCLUSIONS Carbon dioxide pericardial insufflation in open-chamber cardiac surgery does not affect postoperative neurocognitive decline. The most important factor is atheromatous vascular disease.

Isavuconazole as salvage therapy for mucormycosis

Mucormycosis carries a high mortality rate with few therapeutic options available. We describe a man with pulmonary/splenic mucormycosis complicating hypoplastic myelodysplastic syndrome on a background of chronic kidney disease, who achieved a complete response with salvage isavuconazole therapy following intolerance of consecutive courses of liposomal amphotericin and posaconazole therapy.

Safety, feasibility, and effect of remote ischemic conditioning in patients undergoing lung transplantation.

BACKGROUND Primary graft dysfunction (PGD) remains a significant problem after lung transplantation. Data from animal and clinical studies suggest that remote ischemic conditioning (RIC) may reduce ischemia-reperfusion injury in solid organ transplantation. METHODS A pilot randomized controlled trial of 60 patients undergoing bilateral sequential lung transplantation assessed the utility of RIC in attenuating PGD. Treated recipients underwent 3 cycles of lower limb ischemic conditioning before allograft reperfusion. The primary outcome measure was a comparison of the partial pressure of arterial oxygen/fraction of inspired oxygen ratio (P/F ratio) between treatment groups. RESULTS No adverse effects of tourniquet application were observed. The mean lowest P/F ratio during the first 24 hours after transplantation was 271.3 mm Hg in the treatment arm vs 256.1 mm Hg in the control arm (p = 0.46). PGD grade and severity and the rate of acute rejection also showed a tendency to favor the treatment arm. Sub-group analysis demonstrated a significant benefit of treatment in patients with a primary diagnosis of restrictive lung disease, a group at high risk for the development of PGD. RIC was not accompanied by systemic release of high-molecular-weight group box 1. Levels of cytokines, high-molecular-weight group box 1, and endogenous secretory receptor for advanced glycation end products peaked within 2 hours after reperfusion and likely reflected donor organ quality rather than an effect of RIC. CONCLUSIONS RIC did not significantly improve P/F ratios or PGD in this randomized controlled trial. However, encouraging results in this small study warrant a large multicenter trial of RIC in lung transplantation.

Buying time: The use of extracorporeal membrane oxygenation as a bridge to lung transplantation in pediatric patients.

To describe our experience to date of four children with end‐stage lung disease who have been bridged with ECMO to successful lung transplantation in our institution. Between March 2006 and June 2012, a total of 21 pediatric patients successfully underwent lung transplantation within The Alfreds lung transplantation program. This included four children who were bridged on ECMO prior to transplantation according to the “ECMO bridge to transplant” protocol and whose clinical notes and outcomes were reviewed. Lung transplantation is an established life‐saving treatment for patients with severe lung disease, but remains limited due to scarcity of suitable donor organs. This is a particular issue in the pediatric setting, where the smaller child waits disproportionately longer compared with adult patients for size‐matched donor lungs. As ECMO has become more widely accepted, its use as a bridge to lung transplantation in pediatric patients with severe acute lung injury or end‐stage chronic lung disease has been considered. The medical notes from the four pediatric patients were retrospectively reviewed. Our report describes excellent short‐ and medium‐term outcomes in a small number of children who have been bridged to transplant on ECMO.

Fast-track cardiac surgery: application in an Australian setting.

In response to the current state of healthcare in Australia, our unit has employed a fast-track policy for low-risk cardiac surgery patients since January 2000. This study was designed to examine the safety and efficacy of this policy. From July 2001 to June 2004, 342 (23%) of 1,488 patients undergoing cardiac surgery were identified preoperatively as suitable for fast-track recovery. There was a significantly shorter median time to extubation (4 hr vs 9 hr), reduced intensive care unit stay (8 hr vs 26 hr), and a lower rate of readmission to the intensive care unit (0.6% vs 4.2%) for those fast tracked compared to the other patients. The fast-track group had a lower incidence of complications and significantly decreased median length of hospital stay (5 vs 7 days). We concluded that this policy accurately identifies the low-risk cardiac surgery patients suitable for less intensive postoperative recovery.

Invasive Scedosporium sternal osteomyelitis following lung transplant: Cured

Scedosporium is an important pathogen in cystic fibrosis (CF) and post-transplant but rarely causes invasive infection. Treatment remains challenging, particularly due to inherent resistance to multiple antifungal agents. We present a young man with CF who developed invasive sternal and rib infection 10-months following lung transplant. The infection has been clinically and radiologically cured with extensive surgery and triazole therapy. This case highlights the importance of adjunctive surgery in addition to prolonged triazole treatment to manage invasive Scedosporium infections in immunosuppressed patients.

Management of refractory chylothorax in pulmonary lymphangioleiomyomatosis

This case reports the successful management of chylothorax in a non‐transplanted patient with pulmonary lymphangioleiomyomatosis (pLAM). Prolonged initial therapy failed, including total parenteral nutrition, pleural drainage, surgical pleurodesis, and pleurectomy. Commencement of sirolimus 2 mg daily (2 mg alternating days had failed) led to resolution of chylothorax after 20 days. Discontinuation of sirolimus for abdominal surgery led to recurrence of the chylothorax. Reinstitution of sirolimus led to rapid resolution of the effusion, stabilization of lung function, and there has been no recurrence in the ensuing 4 years. We conclude that sirolimus should be considered in the management of pLAM‐related chylothorax, perhaps before surgical intervention.

Survival following resuscitative thoracotomy for combined left ventricle and left atrium ruptures secondary to blunt trauma

Improvements in pre-hospital care and the development of integrated Trauma Systems have streamlined access for the severely injured to sophisticated, specialist Trauma Centre reception and resuscitation. We describe the initial care of a survivor of combined ruptures of the left ventricle and left atrium secondary to blunt injury. This case emphasises the contribution of such a Trauma System in achieving a favourable outcome for a severely injured trauma patient with injuries previously considered non-survivable.