Stephen ralph Large

Dr. Stephen ralph Large


Research Focus & Metrics

Academic Career Length

35Years (1992-Present)

(Calculated once Scilit publication data is synced: current year − year of first publication + 1)

Representative Publications

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1 December 2017 in The Journal of Heart and Lung Transplantation
Verified
Journal Article
Closed access
SMSimon Messer
Simon Messer
APAravinda Page
Aravinda Page
RARichard Axell
Richard Axell
MBMarius Berman
Marius Berman
JHJules Hernández-Sánchez
Jules Hernández-Sánchez
SLStephen ralph Large
Stephen ralph Large

27 December 2018 in American Journal of Transplantation
Verified
Journal Article
Open access
PDF file
CWChristopher J.E. Watson
Christopher J.E. Watson
FHFiona Hunt
Fiona Hunt
SMSimon Messer
Simon Messer
ICIan Currie
Ian Currie
SLStephen ralph Large
Stephen ralph Large
Gabriel C. OniscuGabriel C. Oniscu
Gabriel C. Oniscu
Livers from controlled donation after circulatory death (DCD) donors suffer a higher incidence of non‐function, poor function, and ischemic cholangiopathy. In situ normothermic regional perfusion (NRP) restores a blood supply to the abdominal organs after death using an extracorporeal circulation for a limited period before organ recovery. We undertook a retrospective analysis to evaluate whether NRP was associated with improved outcomes of livers from DCD donors. NRP was performed on 70 DCD donors from which 43 livers were transplanted. These were compared with 187 non‐NRP DCD donor livers transplanted at the same two UK centers in the same period. The use of NRP was associated with a reduction in early allograft dysfunction (12% for NRP vs 32% for non‐NRP livers, p=0.0076), 30‐day graft loss (2% NRP livers vs. 12% non‐NRP livers, p=0.0559), freedom from ischemic cholangiopathy (0% vs. 27% for non‐NRP livers, p<0.0001), and fewer anastomotic strictures (7% vs. 27% non‐NRP, p=0.0041). After adjusting for other factors in a multivariable analysis, NRP remained significantly associated with freedom from ischemic cholangiopathy (p<0.0001). These data suggest that NRP during organ recovery from DCD donors leads to superior liver outcomes compared to conventional organ recovery.

1 December 2020 in The Journal of Heart and Lung Transplantation
Verified
Journal Article
Open access
SMSimon Messer
Simon Messer
SCSendi Cernic
Sendi Cernic
APAravinda Page
Aravinda Page
MBMarius Berman
Marius Berman
PKPradeep Kaul
Pradeep Kaul
SLStephen ralph Large
Stephen ralph Large
In an effort to address the increasing demand for heart transplantation within the United Kingdom (UK), we established a clinical program of heart transplantation from donation after circulatory-determined death (DCD) donors in 2015. After 5 years, we report the clinical early outcomes and impact of the program. This is a single-center, retrospective, matched, observational cohort study comparing outcomes of hearts transplanted from DCD donors from March 1, 2015 to February 29, 2020 with those from matched donation after brain death (DBD) donors at Royal Papworth Hospital (RPH) (Cambridge, UK). DCD hearts were either retrieved using thoracoabdominal normothermic regional perfusion or the direct procurement and perfusion technique. All DBD hearts were procured using standard cold static storage. The primary outcomes were recipient 30-day and 1-year survival. During the 5-year study, DCD heart donation increased overall heart transplant activity by 48% (79 for DCD and 164 for DBD). There was no difference in survival at 30 days (97% for DCD vs 99% for DBD, p = 1.00) or 1 year (91% for DCD vs 89% for DBD, p = 0.72). There was no difference in the length of stay in the intensive care unit (7 for DCD vs 6 for DBD days, p = 0.24) or in the hospital (24 for DCD vs 25 for DBD days, p = 0.84). DCD heart donation increased overall heart transplant activity at RPH by 48%, with no difference in 30-day or 1-year survival in comparison with conventional DBD heart transplantations. DCD heart donation is set to make a dramatic difference in the number of patients who can benefit from heart transplantation.

2 March 2023 in eClinicalMedicine
Verified
Journal Article
Open access
JLJohn Louca
John Louca
MÖMarco Öchsner
Marco Öchsner
ASAshish Shah
Ashish Shah
JHJordan Hoffman
Jordan Hoffman
ADAlexandra Debose-Scarlett
Alexandra Debose-Scarlett
LCLaurens Ceulemans
Laurens Ceulemans
Heart transplantation is an effective treatment offering the best recovery in both quality and quantity of life in those affected by refractory, severe heart failure. However, transplantation is limited by donor organ availability. The reintroduction of heart donation after the circulatory determination of death (DCD) in 2014 offered an uplift in transplant activity by 30%. Thoraco-abdominal normothermic regional perfusion (taNRP) enables in-situ reperfusion of the DCD heart. The objective of this paper is to assess the clinical outcomes of DCD donor hearts recovered and transplanted from donors undergoing taNRP. This was a multicentre retrospective observational study. Outcomes included functional warm ischaemic time, use of mechanical support immediately following transplantation, perioperative and long-term actuarial survival and incidence of acute rejection requiring treatment. 157 taNRP DCD heart transplants, performed between February 2, 2015, and July 29, 2022, have been included from 15 major transplant centres worldwide including the UK, Spain, the USA and Belgium. 673 donations after the neurological determination of death (DBD) heart transplantations from the same centres were used as a comparison group for survival. taNRP resulted in a 23% increase in heart transplantation activity. Survival was similar in the taNRP group when compared to DBD. 30-day survival was 96.8% ([92.5%-98.6%] 95% CI, n = 156), 1-year survival was 93.2% ([87.7%-96.3%] 95% CI, n = 72) and 5-year survival was 84.3% ([69.6%-92.2%] 95% CI, n = 13). Our study suggests that taNRP provides a significant boost to heart transplantation activity. The survival rates of taNRP are comparable to those obtained for DBD transplantation in this study. The similar survival may in part be related to a short warm ischaemic time or through a possible selection bias of younger donors, this being an uncontrolled observational study. Therefore, our study suggests that taNRP offers an effective method of organ preservation and procurement. This early success of the technique warrants further investigation and use. None of the authors have a financial relationship with a commercial entity that has an interest in the subject.

1 July 2018 in The Journal of Heart and Lung Transplantation
Verified
Journal Article
Closed access
SMSimon Messer
Simon Messer
APAravinda Page
Aravinda Page
SCSimon Colah
Simon Colah
RARichard Axell
Richard Axell
BPBarbora Parizkova
Barbora Parizkova
SLStephen ralph Large
Stephen ralph Large

1 January 2018 in Annals of Cardiothoracic Surgery
Verified
Journal Article
Closed access
PDF file
APAravinda Page
Aravinda Page
SMSimon Messer
Simon Messer
SLStephen ralph Large
Stephen ralph Large
Fifty years since the first successful human heart transplant from a non-heart beating donor, this concept of heart transplantation from donation after circulatory determined death (DCD) promises to be one of the most exciting developments in heart transplantation. Heart transplantation has established itself as the best therapeutic option for patients with end-stage heart failure, with the opportunity to provide these patients with a near-normal quality of life. However, this treatment is severely limited by the availability of suitable donor hearts. In recent times, heart transplantation has been limited to using donor hearts from donors following brain stem death. The use of donor hearts from DCD had been thought to be associated with high risk and poor outcomes until recent developments in organ perfusion and retrieval techniques have shown that this valuable resource may provide an answer to the global shortage of suitable donor hearts. With established DCD heart transplant programmes reporting encouraging results, this technique has been shown to be comparable to the current gold standard of donation after brain death (DBD) heart transplantation.