Freeman Hospital

In the original publication [...].

Surveillance of individuals with a familial predisposition to pancreatic ductal adenocarcinoma (PDAC) is likely to increase overall survival. Our objective was to determine the impact of EUROPAC risk-stratification (Family Risk, FR), in such predisposed individuals. Observational study of registered asymptomatic individuals undergoing surveillance for PDAC. Individuals without a known pathogenic variant (PV-), ineligible for genetic assessment in the NHS, in whom significant pancreatic lesions were found, were subjected to additional germline testing. Between January 2000 and April 2025, 893 individuals started surveillance, median age of 52 years. 508 individuals (404 PV- and 104 with a pathogenic variant (PV+)) in the 20 years prior to 2020 without stratification were compared to 385 (269 PV- and 116 PV+) in the five years from 2020 who had FR risk-stratification applied. Four (0·8 %) individuals had actionable pancreatic findings prior to risk stratification vs. 14 (3·6 %), who underwent risk-stratified surveillance (p = 0·001). Pancreatic lesions deemed operable were found in three (0·6 %) and 11 (3 %), p = 0·007, with two (0·4 %) and nine (2 %) undergoing resection, p = 0·009, respectively. PV- individuals with significant findings were subsequently found to contain mutations, many not in the UK genetics test directory, provided the FR was > 30. The median (IQR) time in surveillance prior to a lesion being detected was four (2 - 7) years. Overall, 78 % of EUROPAC detected precursor lesions or pancreatic cancers were stage II or lower. The risk-stratified group (FR) identifies neoplastic pancreatic lesion in individuals, regardless of PV status suggesting the key usefulness of this approach.

The number of children referred for advanced heart failure management is increasing and with it the demand for heart transplant. However, transplantation rates have declined and waiting list mortality is up to 25%. While donation after circulatory death (DCD) heart recovery has increased adult transplant activity significantly, barriers have prevented the same in pediatrics. In the UK and Belgium, we have adopted hypothermic oxygenated perfusion (HOPE) to address this inequity. Preclinical: A porcine DCD-HOPE model was developed to simulate neonatal and infant heart recovery, preservation, and transplantation, including functional assessment. Hearts were recovered from 6 pediatric donors (3 DCD and 3 donation after brainstem death), aged 16 months-13 years), preserved with HOPE and transplanted. For small donors, this required a pediatric research cannula and surgical techniques, such as arch augmentation. In the preclinical model, porcine infant hearts could be successfully recovered, perfused, and transplanted with good cardiac output postbypass. In the clinical series, hearts from donors as small as 9kg were successfully recovered, perfused, and transplanted. For the DCD cohort, median functional warm ischemic time was 19minutes and there was no severe primary graft dysfunction. Survival at follow-up (median 287.5 days) was 100% and echocardiograms showed normal systolic function. There is great need to facilitate DCD heart recovery for infants and neonates. We have reported our outcomes from the world's first and smallest pediatric DCD-HOPE heart transplants and demonstrated that HOPE provides the long-awaited solution for pediatric DCD donation down to even neonatal donors. We call upon clinicians and policymakers to support DCD-HOPE to provide equity for child donors and recipients.

Background.In circulatory death transplantation, time to death (TTD) following withdrawal of life-sustaining treatment is unpredictable. Concerns persist that prolonged TTD may cause ischemic injury, resulting in organ nonuse. We assessed the impact of donor TTD on liver transplant outcomes and utilization.Methods.We used Organ Procurement and Transplantation Network data on adult donors after circulatory death transplants (2010–2025). Multivariable nonlinear (restricted cubic splines) regression models were used to analyze associations. Simulation studies estimated potential increases in liver acceptance rates.Results.In 8489 recipients, short donor TTD was associated with inferior outcome, contrary to popular belief. Prolonged TTD did not show inferior posttransplant outcomes, irrespective of whether normothermic regional perfusion (NRP) was used. Nonlinear modeling (n = 37 447) revealed a sharp decline in utilization once TTD exceeded just 15 min. Given prolonged TTD did not impact outcomes, these declines represent a missed opportunity for organ use. Simulation studies revealed that if surgeons assess organ offers from patients with TTD of 15–30 min identically to those with TTD <10 min, there would have been a 17.1% (95% confidence interval, 15.0%-19.3%) relative increase in utilization, with potentially better outcomes than current practice. In the setting of NRP, short TTD was associated with increased organ nonuse, potentially because of failed viability criteria in damaged livers.Conclusions.Short TTD was associated with inferior posttransplant outcome, challenging the dogma that shorter is better. Prolonged TTD did not negatively impact posttransplant outcomes, irrespective of NRP use. These findings support expanded use of liver donors with prolonged TTD, especially in the era of NRP and advanced perfusion, where viability assessment provides an additional safeguard.

Pain management in acute pancreatitis (AP) is of critical therapeutic and prognostic significance. We aimed to identify patient phenotypes in AP based on pain management strategies and evaluate their prognostic impact. Data from two major international prospective cohort studies of AP patients (PAINAP study, n = 2119 and APPRENTICE study, n = 1544) from 141 centers worldwide were collated. Demographic data and analgesic use (within 72 h of presentation) were used for latent class analysis of binary analgesic data. The number of clusters was determined by minimisation of Bayesian information criterion. Cluster assignment and AP outcomes were interrogated with multivariable mixed-effects logistic regression. Overall, 3469 patients (median age 52; 47 % female) were analysed. There were 1015 (29.2 %) patients that had moderately severe to severe AP. Within the first 72 h, 494 (14.2 %) patients received non-steroidal anti-inflammatory drugs (NSAIDs), 1410 (40.6 %) weak opioids, 1347 (14.2 %) strong opioids, and 48 (1.4 %) epidural analgesia. There were significant variations in analgesic prescribing patterns across centers (p < 0.001, interclass correlation coefficient 43.8 %). Latent class analysis identified 5 unique patient clusters: early NSAIDs use, minimal analgesic use, strong opioid use, early multimodal analgesia use, and early weak opioid use. The cluster characterized by early NSAIDs was associated with non-severe AP (adjusted odds ratio 0.64, 95 % confidence interval 0.44-0.93, p = 0.02), which could suggest that the use of NSAIDs was perhaps driven by milder pain severity. Unique clusters in the management of pain in AP were identified, with associations to severity of AP. Substantial centre-level variations exist in the patterns of analgesic prescribing globally, contributing to variations in outcomes.