Defatting of donor transplant livers during normothermic perfusion-a randomised clinical trial: study protocol for the DeFat study.

BACKGROUND: Liver disease is the third leading cause of premature death in the UK. Transplantation is the only successful treatment for end-stage liver disease but is limited by a shortage of suitable donor organs. As a result, up to 20% of patients on liver transplant waiting lists die before receiving a transplant. A third of donated livers are not suitable for transplant, often due to steatosis. Hepatic steatosis, which affects 33% of the UK population, is strongly associated with obesity, an increasing problem in the potential donor pool. We have recently tested defatting interventions during normothermic machine perfusion (NMP) in discarded steatotic human livers that were not transplanted. A combination of therapies including forskolin (NKH477) and L-carnitine to defat liver cells and lipoprotein apheresis filtration were investigated. These interventions resulted in functional improvement during perfusion and reduced the intrahepatocellular triglyceride (IHTG) content. We hypothesise that defatting during NMP will allow more steatotic livers to be transplanted with improved outcomes. METHODS: In the proposed multi-centre clinical trial, we will randomly assign 60 livers from donors with a high-risk of hepatic steatosis to either NMP alone or NMP with defatting interventions. We aim to test the safety and feasibility of the defatting intervention and will explore efficacy by comparing ex-situ and post-reperfusion liver function between the groups. The primary endpoint will be the proportion of livers that achieve predefined functional criteria during perfusion which indicate potential suitability for transplantation. These criteria reflect hepatic metabolism and injury and include lactate clearance, perfusate pH, glucose metabolism, bile composition, vascular flows and transaminase levels. Clinical secondary endpoints will include proportion of livers transplanted in the two arms, graft function; cell-free DNA (cfDNA) at follow-up visits; patient and graft survival; hospital and ITU stay; evidence of ischemia-reperfusion injury (IRI); non-anastomotic biliary strictures and recurrence of steatosis (determined on MRI at 6 months). DISCUSSION: This study explores ex-situ pharmacological optimisation of steatotic donor livers during NMP. If the intervention proves effective, it will allow the safe transplantation of livers that are currently very likely to be discarded, thereby reducing waiting list deaths. TRIAL REGISTRATION: ISRCTN ISRCTN14957538. Registered in October 2022.

Are vegans being overlooked in our prescribing practices: An orthopaedic perspective from Bristol, United Kingdom.

Aim: Bristol is considered the vegan capital of the UK. The UK vegan index reveals that Bristol has 360,000 Google searches each month for Vegan content. However, the possible animal source of the medications we prescribe is not commonly contemplated. Medications in the UK must pass through animal trials prior to licensing and therefore cannot be vegan. There are, alternatives available for some medications, that do not contain animal products. The aim of this study is to review the presence of content of animal origin (CAO) in common medicines in Trauma and Orthopaedics (T&O) and explore alternatives. Methods: We evaluated the presence and source of CAO in commonly used medications in T&O practice. The British National Formulary (BNF), our local pharmacy guidelines and the online Summary of Product Characteristics (SPCs) for the medications were reviewed. We also assessed the suitability of current COVID-19 vaccines for patients who have reservations against CAO. Results: All unfractionated or standard heparin is porcine in origin; Fondaparinux is a simple alternative. Cholecalciferol (vitamin D3) manufacture involves the use of lanolin from sheep's wool. Vitamin D2 (ergocalciferol) is an alternative with no CAO. All widely available Covid-19 vaccines in the UK are suitable for administration to vegans and all religious faiths. Propofol, widely used as an anaesthetic agent, contains egg proteins. Conclusion: Disclosure of animal content would help patients make informed choices. With an increasingly informed population and ethnic diversity, we should be aware of the drugs that may contain animal products so that we can offer alternatives. Sometimes, pharmaceutical companies cannot guarantee or differentiate the specific sources of animal-derived ingredients, as various suppliers are used in the manufacturing process and the sources can change on a regular basis. Patients are more likely to adhere to prescribed medicines if they have been involved in prescribing decisions.

Perioperative multimodal analgesic injection for patients with adolescent idiopathic scoliosis undergoing posterior spinal fusion surgery.

PURPOSE: This retrospective cohort study compared postoperative as-needed (PRN) opioid consumption pre and postimplementation of a perioperative multimodal analgesic injection composed of ropivacaine, epinephrine, ketorolac, and morphine in patients undergoing posterior spinal fusion (PSF) for adolescent idiopathic scoliosis (AIS). Secondary outcomes include pain score measurements, time to ambulation, length of stay, blood loss, 90-day complication rate, operating room time, nonopioid medication usage, and total inpatient medication cost before and after the initiation of this practice. METHODS: Consecutive patients weighing ≥ 20 kg who underwent PSF for a primary diagnosis of AIS between January 2017 and December 2020 were included. Data from 2018 were excluded to account for standardization of the practice. Patients treated in 2017 only received PCA. Patients treated in 2019 and 2020 only received the injection. Excluded were patients who had any diagnoses other than AIS, allergies to any of the experimental medications, or who were nonambulatory. Data were analyzed utilizing the two-sample t-test or Chi-squared test as appropriate. RESULTS: Results of this study show that compared with 47 patients treated postoperatively with patient-controlled analgesia (PCA), 55 patients treated with a multimodal perioperative injection have significantly less consumption of PRN morphine equivalents (0.3 mEq/kg vs. 0.5 mEq/kg; p = 0.02). Furthermore, patients treated with a perioperative injection have significantly higher rates of ambulation on postoperative day 1 compared with those treated with PCA (70.9 vs. 40.4%; p = 0.0023). CONCLUSION: Administration of a perioperative injection is effective and should be considered in the perioperative protocol in patients undergoing PSF for AIS. LEVEL OF EVIDENCE: Therapeutic Level III.

What is the purpose of clinical trial monitoring?

BACKGROUND: The sources of information on clinical trial monitoring do not give information in an accessible language and do not give detailed guidance. In order to enable communication and to build clinical trial monitoring tools on a strong easily communicated foundation, we identified the need to define monitoring in accessible language. METHODS: In a three-step process, the material from sources that describe clinical trial monitoring were synthesised into principles of monitoring. A poll regarding their applicability was run at a UK national academic clinical trials monitoring meeting. RESULTS: The process derived 5 key principles of monitoring: keeping participants safe and respecting their rights, having data we can trust, making sure the trial is being run as it was meant to be, improving the way the trial is run and preventing problems before they happen. CONCLUSION: From the many sources mentioning monitoring of clinical trials, the purpose of monitoring can be summarised simply as 5 principles. These principles, given in accessible language, should form a firm basis for discussion of monitoring of clinical trials.