Portal vein thrombosis (PVT) complicates up to a third of patients with cirrhosis and is associated with variceal bleeding, refractory ascites, and challenges at liver transplantation. Management has evolved from selective anticoagulation to broader use of endovascular therapies, especially transjugular intrahepatic portosystemic shunt (TIPS) and portal vein recanalisation strategies. In this narrative review, we summarise the current evidence for anticoagulation, thrombolysis, TIPS, and surgery, and compare major society guidelines. Meta-analyses in cirrhosis show that anticoagulation increases recanalisation and reduces thrombus progression without increasing major bleeding and may lower variceal bleeding risk. Endovascular meta-analysis demonstrates high feasibility of TIPS for PVT ( 95
Ex situ normothermic machine perfusion (NMP) is rapidly emerging as a novel platform for testing therapeutics in human donor livers. Recently, perfusion of explanted patient livers was achieved, raising the possibility of using these diseased organs to increase the fidelity and resolution of drug testing and development. Here, we provide proof-of-principle for the feasibility of this approach in the context of gene therapy. We report the first successful administration of adeno-associated virus serotype 8 (AAV8) vector treatment in the explanted liver of a 34-year-old patient with mitochondrial neurogastrointestinal encephalomyopathy (MNGIE), using machine perfusion. MNGIE is caused by mutations in the thymidine phosphorylase (TYMP) gene, leading to nucleoside accumulation. The patient's liver was split into anatomical left and right lobes and perfused using separate machine perfusion devices. Prior to treatment, nucleoside accumulation was observed in the perfusate of both lobes, recapitulating the cardinal feature of MNGIE. An AAV8 vector carrying the human TYMP gene was administered in the left lobe with the right serving as a control. AAV8 gene therapy resulted in successful vector uptake, with complete nucleoside clearance within 6 days of administration. Our results constitute the first demonstration of the efficacy of gene therapy for MNGIE in a human organ and provide proof-of-principle for using machine perfusion as a new strategy for disease modelling and testing novel therapeutics, e.g. gene therapy, in explanted livers.
The role of hepatic venous pressure gradient (HVPG) measurement in risk stratification before liver resection is an ongoing area of debate. This study examines the impact of preoperative HVPG levels on overall survival (OS)/time to recurrence (TTR) and postoperative complications after hepatic resection of hepatocellular carcinoma (HCC). Thirty-eight HCC patients undergoing HVPG measurement before liver resection at Cambridge University Hospitals NHS Foundation Trust between January 2014 and April 2022 were retrospectively analysed. Statistical analysis comprised univariable/multivariable Cox/logistic regression to identify risk factors of reduced OS/TTR or 90-day post-resection complications and Kaplan-Meier estimator, log-rank, chi-squared, Fisher's exact, and Mann-Whitney U test, or Student's t-test for survival/subgroup analysis. The median HPVG was 6 (range: 0-14) mmHg. The HVPG was an independent risk factor for poorer TTR in the overall cohort (cut-off: >= 7.5 mmHg (17.18/43.81 months; P = 0.009)). In the subgroup analysis of cirrhotic patients (N = 29 (76%)), HVPG was additionally an independent risk factor for lower OS (cut-off:>= 8.5 mmHg [44.39/76.84 months; P = 0.012]). The HVPG had no impact on OS/TTR in non-cirrhotic patients (N = 9 (24%)), nor was it associated with postoperative complications in any cohort. In conclusion, preoperative HVPG levels are useful predictors for TTR and OS in cirrhotic HCC patients undergoing hepatic resection.
Vascular Ehlers-Danlos Syndrome (vEDS) is a rare and potentially life-threatening inherited connective tissue disorder. Patients with vEDS can present with spontaneous arterial dissections and ruptured aneurysms. There are previous reports of large artery dissections and vessel rupture following conventional catheter diagnostic angiography. We present the case of a patient with vEDS who had a spontaneous carotid-cavernous fistula (CCF) and visceral aneurysms, associated with a normal variant of corona mortis. A CCF was successfully treated with a transvenous approach with detachable coils.
Deaths from the majority of cancers are falling globally, but the incidence and mortality from hepatocellular carcinoma (HCC) is increasing in the United Kingdom and in other Western countries. HCC is a highly fatal cancer, often diagnosed late, with an incidence to mortality ratio that approaches 1. Despite there being a number of treatment options, including those associated with good medium to long-term survival, 5-year survival from HCC in the UK remains below 20%. Sex, ethnicity and deprivation are important demographics for the incidence of, and/or survival from, HCC. These clinical practice guidelines will provide evidence-based advice for the assessment and management of patients with HCC. The clinical and scientific data underpinning the recommendations we make are summarised in detail. Much of the content will have broad relevance, but the treatment algorithms are based on therapies that are available in the UK and have regulatory approval for use in the National Health Service.
OBJECTIVE:To investigate the behaviour of common healthcare related objects in a 3 tesla (T) MRI (magnetic resonance imaging) scanner, examining their ability to self-propel towards the scanner bore and their potential for tissue penetration.DESIGN:Prospective in situ experimental study.SETTING:Clinical 3 T MRI scanner. Customised rig designed and built to guide objects towards the scanner bore.PARTICIPANTS:12 categories of objects commonly found in hospitals, or on patients or healthcare professionals, or near an MRI scanning room. Human tissue penetration simulated with ballistic gel (Federal Bureau of Investigation and North Atlantic Treaty Organisation graded).MAIN OUTCOME MEASURES:SANTA (site where applied newtonian mechanics triggers acceleration) measurements and depth of tissue penetration of the objects.RESULTS:SANTA measurements ranged from 0 cm for the 20 pence, 50 pence, and £2 coins to 152-161 cm for a knife and the biscuit tins. One penny, two pence, five pence, and 10 pence coins showed self-propulsion and acceleration towards the scanner bore at a distance >100 cm from the gantry entry point. Linear regression analysis showed no apparent correlation between the weight of the objects and their SANTA measurements (R2<0.1). Only five objects penetrated the ballistic gel (simulated human tissue). The deepest penetration was by the knife (5.5 cm), closely followed by the teaspoon (5.0 cm), fork (4.0 cm), spoon (3.5 cm), and a 10 pence coin (0.5 cm). Although the biscuit tins did not penetrate the simulated human tissue, they exerted substantial impact force which could potentially cause bone fractures. A smartphone, digital thermometer, metallic credit card, and pen torch remained fully functional after several passes into the MRI scanner. No discernible loss of image quality for the MRI scanner after the experiments was found.CONCLUSIONS:The study highlights the potential for harm (major tissue damage and bone fractures) when commonly found objects in a healthcare setting are unintentionally brought into the MRI scanner room. Patients and healthcare professionals need to be aware of the dangers associated with bringing ferromagnetic objects into the MRI environment.
The Healthcare Safety Investigation Branch (HSIB) report, Failures in communication or follow-up of unexpected significant radiological findings 1 Healthcare Safety Investigation BranchFailures in communication or follow up of unexpected significant radiological findings. https://www.hsib.org.uk/documents/135/hsib_report_failures_communication_follow_up_unexpected_significant_radiological_findi.pdfDate: 2019 Google Scholar highlights the case of a patient with lung cancer on a chest radiograph that was not reported and acted upon promptly by several different clinical teams leading to delayed diagnosis and poor outcome. This case is by no means isolated. Similar incidents still occur despite a well-established electronic notification system and the referrer being notified in a timely fashion about the abnormal report. There is a clear need to address some of the areas of concern regarding the existing result notification system to ensure there are no opportunities for missed or delayed communication and action. To achieve this, the process and the responsibility to act on abnormal radiology findings needs to be clearly defined and standardised across multiple specialties. A fail-safe result notification system will require oversight and facilitation by healthcare organisations.
Interventional radiology is a key service in all hospitals in the UK.Interventional radiology units vary in size depending on the size of the hospital, the services provided by the hospital and their proximity to other units.All patients should have access to emergency interventional radiology procedures whenever they require them.This will require a network arrangement between hospitals in some cases.An out-of-hours interventional radiology oncall rota of at least one in six is the minimum standard that should exist.A wide number of clinical conditions are treated by interventional radiologists and the number of procedures grows year on year.Some basic interventional radiology procedures can also be performed by appropriately trained allied health professionals.Interventional radiologists should aspire to take primary responsibility for their patients and should adopt all tenets &
Effective communication is vital in ensuring patient safety and is an important measure of the quality of healthcare. Poor test-result management has long been identified as a high-priority in improving patient safety by the World Health Organization (WHO).1 Failure to follow-up pathology and imaging test results is frequently seen and has been reported in 20–62% of inpatients, up to 75% of patients in an emergency department,2 and up to 65% in ambulatory care.3 The consequences of delay or failure in the process of communication of results and acting on results cannot only be catastrophic for the patient, but also wastes scarce resources and can result in malpractice claims.
Background Capnography has been associated with a reduced incidence of events related to respiratory compromise during procedural sedation. Methods A prospective service evaluation was conducted at a large United Kingdom (UK) teaching hospital to assess the impact of capnography on patient safety within four speciality services: bronchoscopy, endoscopy, interventional cardiology, and interventional radiology. Events were defined as provided by the World Society of Intravenous Anaesthesia. One thousand four hundred one patients were enrolled in the evaluation, with 666 patients before and 735 after implementation of capnography. Data was entered as a convenience sample on site in an offline data-collection tool. Results were assessed for the relative reduction in the incidence and resulting adjusted odds ratio for the combined incidence of oxygen desaturation (75–90% for <60s), severe oxygen desaturation (<75% at any time) or prolonged oxygen desaturation (<90% for >60s), bradycardia (>25% from baseline) and tachycardia (>25% from baseline). The adjusted odds ratio was controlled for both procedure and patient characteristics. Results After implementation of capnography, a significant reduction (43.2%, p ≤ 0.05) in adverse events was observed: 147 adverse events occurred during 666 procedures without capnography compared with 93 adverse events that occurred during 735 procedures with capnography. The adjusted odds ratio for the occurrence of the target adverse events was 0.57 (95% CI: 0.42–0.77). Multivariable linear regression indicated that capnography was a significant predictor ( p 0.001) of reduced adverse events. Conclusion These results suggest improved patient safety following capnography implementation.
Background: Surgical resection, where appropriate, remains one of the best treatment op-tions for hepatocellular carcinoma (HCC), however outcomes can be compromised by the development of liver failure. We reviewed our experience of liver resection for HCC pa-tients to identify factors that may predict the development of post-hepatectomy liver failure (PHLF) and survival.Methods: A single centre retrospective cohort study. Data was collected between 1999 and 2017 from all patients undergoing HCC resection in a tertiary university hospital from electronic medical records. PHLF was defined as per the International Study Group for Liver Surgery criteria. Variables with p < 0.15 on univariate analysis were included in a multi-variate binary logistic regression model. Kaplan-Meier analyses were used to determine correlations with overall survival (OS) and disease-free survival (DFS), and variables with p < 0.15 on univariate analysis selected for a step-down Cox proportional hazard regression model.Results: Overall, 120 patients underwent liver resection within the study period, of which 22 (18%) developed PHLF. Patients with normal INR <1.20 at day 2 did not develop PHLF whereas patients with INR >1.60 were at significant risk. Resection of multiple tumours (odds ratio 21.63, p = 0.002) and deranged postoperative day 2 INR>1.6 (odds ratio 21.05, p < 0.0001) were identified as independent prognostic markers of PHLF.Conclusion: The use of INR measurement at day 2 predicts PHLF and may enable us to objectively identify and stratify patients who may be eligible for enhanced recovery pro-grams from those who will merit close monitoring in high dependency areas.Crown Copyright (c) 2022 Published by Elsevier Ltd on behalf of Royal College of Surgeons of Edinburgh (Scottish charity number SC005317) and Royal College of Surgeons in Ireland. All rights reserved.
Introduction: Capnography is part of monitoring for procedural sedation in selected endoscopic procedures at Cambridge University Hospitals NHS Foundation Trust and shows potential benefit through earlier detection of respiratory compromise. Aims and objectives: Gastroenterology (GI), interventional cardiology (IC), and vascular access (VA), respiratory medicine (RM) services undertook a quality of care improvement initiative to quantify the effect of using capnography as part of standard monitoring, on procedure safety. Methods: The cumulative endpoint was the incidence of oxygen desaturation (<75% any duration, 75-90% <60 seconds(s), <90% >60s), bradycardia, and tachycardia (>25% change from baseline). We targeted a 20% reduction in this cumulative endpoint post capnography implementation. Data was collected between December 2017 and January 2020 and results were collected on-site in an Excel-based data tool. No patient identifiers were recorded. Results: Data from 1,401 procedures across the GI, IC, and RM services were collected. The first 666 procedures were pre-capnography, and following 735 procedures post-capnography. A 42% (p<0.05) reduction in the incidence of the cumulative endpoint was recorded with capnography. Of the 129 bronchoscopic procedures, there were 0.59 events in the 73 pre-capnography group and 0.46 events in the 56 post-capnography group. This is a 21% percent reduction in the cumulative endpoint. Conclusions: With capnography monitoring, a 21% reduction in adverse events was recorded during RM procedures. GI, IC, and RM services support including capnography monitoring in the hospital’s sedation guidelines.
Organoid technology holds great promise for regenerative medicine but has not yet been applied to humans. We address this challenge using cholangiocyte organoids in the context of cholangiopathies, which represent a key reason for liver transplantation. Using single-cell RNA sequencing, we show that primary human cholangiocytes display transcriptional diversity that is lost in organoid culture. However, cholangiocyte organoids remain plastic and resume their in vivo signatures when transplanted back in the biliary tree. We then utilize a model of cell engraftment in human livers undergoing ex vivo normothermic perfusion to demonstrate that this property allows extrahepatic organoids to repair human intrahepatic ducts after transplantation. Our results provide proof of principle that cholangiocyte organoids can be used to repair human biliary epithelium.
Purpose The purpose of this study was to evaluate the predictive value of a 'Modified Karnofsky Scoring System' on outcomes and provide real-world data regarding the UK practice of biliary interventions. Materials and Methods A prospective multi-centred cohort study was performed. The pre-procedure modified Karnofsky score, the incidence of sepsis, complications, biochemical improvement and mortality were recorded out to 30 days post procedure. Results A total of 292 patients (248 with malignant lesions) were suitable for inclusion in the study. The overall 7 and 30 day mortality was 3.1% and 16.1%, respectively. The 30 day sepsis rate was 10.3%. In the modified Karnofsky 'high risk' group the 7 day mortality was 9.7% versus 0% for the 'low risk' group (p = 0.002), whereas the 30 day mortality was 28.8% versus 13.3% (p = 0.003). The incidence of sepsis at 30 days was 19% in the high risk group versus 3.3% at the low risk group (p = 0.001) Conclusion Percutaneous biliary interventions in the UK are safe and effective. Scoring systems such as the Karnofsky or the modified Karnofsky score hold promise in allowing us to identify high risk groups that will need more careful consideration and enhanced patient informed consent but further research with larger studies is warranted in order to identify their true impact on patient selection and outcomes post biliary interventions.
Introduction Physician-led sedation is commonly employed for selected endoscopic procedures. There is still an open question around the optimal patient monitoring strategy during such procedures. Use of additional capnography has been shown to be associated with fewer patient respiratory compromise events than pulse oximetry alone. To quantify and explore the impact of capnography on patient safety, a quality improvement initiative was undertaken for gastrointestinal (GI), interventional cardiology (IC), vascular access (VA), and respiratory medicine (RM) clinical services at a large UK teaching hospital. Methods Four target events as defined by the world Society for Intravenous Anaesthesia (SIVA) tool were determined as the cumulative primary outcome after a review of available literature. These events were: Oxygen desaturation (75-90%) for <60s, severe (<75% at any time) or prolonged (<90% for >60s) oxygen desaturation, bradycardia (>25% increase from baseline), and tachycardia (>25% decrease from baseline).The design was preand post-implementation of capnography monitoring. A 20% reduction in this cumulative endpoint was agreed upon to be the quality improvement threshold. Data on procedures featuring procedural sedation were collected as a convenience sample between December 2017 and January 2020. The results were entered on-site in an Excel based data collection tool. No patient identifiers were recorded. Results The data from 1,401 procedures across the GI, IC, and RM services were collected. The first 666 procedures were pre-capnography (baseline), with the subsequential 735 post-capnography implementation (capnography). GI represented 601 of the procedures, with 262 collected at baseline and 339 with capnography. Over the 1,401 procedures, a 42% reduction in the incidence of the composite endpoint was recorded. The adjusted odds ratio was estimated at 0.57 (95% confidence interval (CI): 0.42 0.77). For the department of GI, 20 events were observed in the baseline procedures (0.076 events per procedure), and for the capnography arm 12 (0.035 events per procedure), corresponding with a 53.9% percent reduction in the composite endpoint. Odds ratios were decreased for all American Society of Anesthesiologists (ASA) levels, with ASA III patients receiving capnography being associated with the lowest odds ratio [0.24 (95% CI: 0.06-0.94)] for the composite primary outcome compared to baseline. Conclusions Implementing capnography monitoring led to a 42% overall and a 53.9% GI-specific reduction in the composite outcome patient safety events. Participating services support capnography monitoring being added to the hospital’s sedation guidelines. More data are required to explore whether reduction in more rare but severe patient outcomes can be realised with use of capnography monitoring.