Procurement and ex-situ perfusion of isolated slaughterhouse-derived livers as a model of donors after circulatory death

Ex-situ machine perfusion (MP) techniques are increasingly used in clinical settings, especially on grafts derived from donors after cardiac death (DCD). However, comprehension of biological effects elicited during MP are largely unknown and a substantial number of animal studies are presently focused on this topic. The aim of the present study was to describe a model of DCD based on ex-situ perfusion of liver grafts derived from animals dedicated to food production. Procurement took place within a slaughterhouse facility. A clinically fashioned closed circuit normothermic MP (NMP) was built up. Autologous blood-enriched perfusion fluid was adopted. Perfusate and tissue samples were collected to asses NMP functionality. Grafts were classified as transplantable (LT-G) or not (n-LT) according to clinical criteria, while histopathological analysis was used to confirm graft viability. After cold storage, the liver grafts were connected to the NMP. During the rewarming phase, temperature and flows were progressively increased to reach target values. At the end of NMP, 4 grafts were classified as LT-G and 3 nLT-G. Histology confirmed absence of major damage in LT-G, while diffuse necrosis appeared in nLT-G. Interestingly, in nLT-G an early impairment of hepatocyte respiratory chain, leading to cell necrosis and graft non-viability, was documented for the first time. These parameters, together with indocyanine-green dye and citrate clearance could contribute to graft evaluation in clinical settings. In conclusion, this model provides a promising and reproducible method to replace dedicated experimental animals in DCD and MP research, in line with the 3Rs principles

Sequential use of normothermic regional and ex-situ machine perfusion in DCD liver transplant

In Italy, 20 minutes of continuous, flat-line electrocardiogram are required for declaration of death. In the setting of organ donation after cardiocirculatory death (DCD), prolonged warm ischemia time prompted introduction of abdominal normothermic regional perfusion (NRP) followed by post-procurement, ex-situ machine perfusion. This was a retrospective review of DCD liver transplantations performed at two centers using sequential NRP and ex-situ machine perfusion. From January 2018 to April 2019, 34 DCD donors were evaluated. Three (8.8%) were discarded before NRP, 11 (32.4%) based on NRP parameters (n=1, 3.0%), liver macroscopic appearance at procurement and/or biopsy results (n=9, 26.5%), or severe macroangiopathy at back table evaluation (N=1, 3.0%). Twenty grafts (58.8%) (12 uncontrolled DCD, 8 controlled DCD) were considered eligible for LT, procured and perfused ex-situ (9 normothermic and 11 dual hypothermic machine perfusion). Eighteen (52.9%; 11 uncontrolled) were eventually transplanted. Median (IQR) no-flow time was 32.5 (30-39) minutes, while median functional-warm ischemia time was 52.5 (47-74) minutes (controlled DCD) and median low-flow time 112 (105-129) minutes (uncontrolled DCD). There was no primary non-function, while post-reperfusion syndrome occurred in 8 (44%) recipients. Early allograft dysfunction happened in 5 (28%) patients, while acute kidney injury in 5 (28%). After a median follow up of 15.1 (9.5-22.3) months, one case of ischemic-type biliary lesion and one patient death were reported. DCD liver transplantation is feasible even with the 20-minute no-touch rule. Strict normothermic regional perfusion and ex-situ machine perfusion selection criteria are needed to optimize post-operative results

Global Incidence and Risk Factors Associated With Postoperative Urinary Retention Following Elective Inguinal Hernia Repair

Importance Postoperative urinary retention (POUR) is a well-recognized complication of inguinal hernia repair (IHR). A variable incidence of POUR has previously been reported in this context, and contradictory evidence surrounds potential risk factors.Objective To ascertain the incidence of, explore risk factors for, and determine the health service outcomes of POUR following elective IHR.Design, Setting, and Participants The Retention of Urine After Inguinal Hernia Elective Repair (RETAINER I) study, an international, prospective cohort study, recruited participants between March 1 and October 31, 2021. This study was conducted across 209 centers in 32 countries in a consecutive sample of adult patients undergoing elective IHR.Exposure Open or minimally invasive IHR by any surgical technique, under local, neuraxial regional, or general anesthesia.Main Outcomes and Measures The primary outcome was the incidence of POUR following elective IHR. Secondary outcomes were perioperative risk factors, management, clinical consequences, and health service outcomes of POUR. A preoperative International Prostate Symptom Score was measured in male patients.Results In total, 4151 patients (3882 male and 269 female; median [IQR] age, 56 [43-68] years) were studied. Inguinal hernia repair was commenced via an open surgical approach in 82.2% of patients (n = 3414) and minimally invasive surgery in 17.8% (n = 737). The primary form of anesthesia was general in 40.9% of patients (n = 1696), neuraxial regional in 45.8% (n = 1902), and local in 10.7% (n = 446). Postoperative urinary retention occurred in 5.8% of male patients (n = 224), 2.97% of female patients (n = 8), and 9.5% (119 of 1252) of male patients aged 65 years or older. Risk factors for POUR after adjusted analyses included increasing age, anticholinergic medication, history of urinary retention, constipation, out-of-hours surgery, involvement of urinary bladder within the hernia, temporary intraoperative urethral catheterization, and increasing operative duration. Postoperative urinary retention was the primary reason for 27.8% of unplanned day-case surgery admissions (n = 74) and 51.8% of 30-day readmissions (n = 72).Conclusions The findings of this cohort study suggest that 1 in 17 male patients, 1 in 11 male patients aged 65 years or older, and 1 in 34 female patients may develop POUR following IHR. These findings could inform preoperative patient counseling. In addition, awareness of modifiable risk factors may help to identify patients at increased risk of POUR who may benefit from perioperative risk mitigation strategies