ABSTRACT
PURPOSE: Lower gastrointestinal bleeding (LGIB) is common and risk stratification scores can guide clinical decision-making. There is no robust risk stratification tool specific for LGIB, with existing tools not routinely adopted. We aimed to develop and validate a risk stratification tool for LGIB. METHODS: Retrospective review of LGIB admissions to three centres between 2010 and 2018 formed the derivation cohort. Using regressional analysis within a machine learning technique, risk factors for adverse outcomes were identified, forming a simple risk stratification score-The Birmingham Score. Retrospective review of an additional centre, not included in the derivation cohort, was performed to validate the score. RESULTS: Data from 469 patients were included in the derivation cohort and 180 in the validation cohort. Admission haemoglobin OR 1.07(95% CI 1.06-1.08) and male gender OR 2.29(95% CI 1.40-3.77) predicted adverse outcomes in the derivation cohort AUC 0.86(95% CI 0.82-0.90) which outperformed the Blatchford 0.81(95% CI 0.77-0.85), Rockall 0.60(95% CI 0.55-0.65) and AIM65 0.55(0.50-0.60) scores and in the validation cohort AUC 0.80(95% CI 0.73-0.87) which outperformed the Blatchford 0.77(95% CI 0.70-0.85), Rockall 0.67(95% CI 0.59-0.75) and AIM 65 scores 0.61(95% CI 0.53-0.69). The Birmingham Score also performs well at predicting adverse outcomes from diverticular bleeding AUC 0.87 (95% CI 0.75-0.98). A score of 7 predicts a 94% probability of adverse outcome. CONCLUSION: The Birmingham Score represents a simple risk stratification score that can be used promptly on patients admitted with LGIB.
Subject(s)
Clinical Decision Rules , Gastrointestinal Hemorrhage/diagnosis , Adolescent , Adult , Aged , Aged, 80 and over , Clinical Decision-Making , England , Female , Gastrointestinal Hemorrhage/etiology , Gastrointestinal Hemorrhage/therapy , Humans , Male , Middle Aged , Predictive Value of Tests , Prognosis , Reproducibility of Results , Retrospective Studies , Risk Assessment , Risk Factors , Triage , Young AdultABSTRACT
In renal transplantation, ischemia reperfusion injury impairs early graft function and can reduce long term graft survival. Hydrogen has antioxidant and anti-inflammatory properties that can reduce the effects of ischemic injury. The aim of this study was to examine the effects of hydrogen gas administered during reperfusion in a preclinical model of kidney ischemia reperfusion injury. Porcine kidneys underwent 15 min of warm ischemia followed by 22 h of cold ischemia. They were then reperfused for 6 h with whole autologous blood on an ex vivo reperfusion circuit. Paired kidneys were randomized to control (n = 6) (25% oxygen, 5% carbon dioxide, 70% nitrogen) or hydrogen (n = 6) (2% hydrogen, 25% oxygen, 5% carbon dioxide, 68% nitrogen) groups. Tissue, urine, and blood samples were collected at baseline and hourly throughout the reperfusion period. Baseline measurements were similar across groups. Following perfusion, there was no significant difference between control and hydrogen groups in urine output (693 mL vs. 608 mL, P = 0.86), renal blood flow (105.9 vs. 108 mL/min/100g, P = 0.89), acid-base homeostasis, or creatinine clearance. There was a significant increase in cytokine levels from baseline to 6 h in both groups (IL-1ß P = 0.002; IL-6 P = 0.004; IL-8 P = 0.002). However, there were no significant differences in levels of inflammatory cytokines (IL1ß, IL-6, and IL-8) between the groups. The administration of hydrogen gas did not improve renal function, reduce oxidative damage, or inflammation during the reperfusion of ischemically damaged kidneys.
Subject(s)
Hydrogen/therapeutic use , Reperfusion Injury/therapy , Animals , Cold Ischemia , Disease Models, Animal , Kidney/physiopathology , Kidney Transplantation , Oxidative Stress , Renal Circulation , Reperfusion Injury/blood , Reperfusion Injury/physiopathology , Reperfusion Injury/urine , Swine , Warm IschemiaABSTRACT
Hepatocellular carcinoma (HCC) prognosis remains dismal due to late-stage diagnosis; surveillance has been demonstrated to increase early diagnosis rates and receipt of curative treatment. Acknowledging limitations in the evidence base for HCC surveillance, international professional bodies reiterate the recommendation for biannual HCC surveillance and NHS England supports measures aimed to increase surveillance uptake. The current ad hoc provision of HCC surveillance is prone to failures, evident by low surveillance uptake and high numbers of patients being diagnosed outside of surveillance. We discuss challenges related to HCC surveillance in the UK and potential solutions to addressing them. We highlight the requirements of a consistent and effective national surveillance process, and suggest pathways on how this can be achieved.
ABSTRACT
BACKGROUND: Biannual ultrasound (US) is recommended for hepatocellular carcinoma (HCC) surveillance in patients with cirrhosis. However, US has limited sensitivity for early-stage HCC, particularly in overweight cohorts, where hepatic visualisation is often inadequate. Currently there are no robust imaging surveillance strategies in patients with inadequate US visualisation. We investigated the ability of non-contrast, abbreviated magnetic resonance imaging (aMRI) to adequately visualise the liver for HCC surveillance in patients with previously inadequate US. METHODS: Patients undergoing US surveillance, where liver visualisation was inadequate (LI-RADS VIS-B and VIS-C), were prospectively recruited. Patients underwent non-contrast T2-weighted and diffusion-weighted aMRI. The images were reviewed and reported by an expert liver radiologist. Three independent, blinded radiologists assessed the aMRI visualisation quality using a binary score assessing five parameters (parenchymal definition, vascular definition, coverage of the liver, uniformity of liver appearance and signal-to-noise ratio). RESULTS: Thirty patients completed the aMRI protocol. The majority (90%) had underlying cirrhosis and were overweight (93.3%), with 50% obese and 20% severely obese. A total of 93.3% of the aMRI scans were of satisfactory quality. Six patients (20%) had hepatic abnormalities detected with aMRI that were not seen on their US: one HCC, one haemangioma and three clinically insignificant lesions. For the aMRI visualisation quality assessment, the coverage of the liver, vascular definition and parenchymal definition were consistently rated to be of sufficient quality by all three radiologists. CONCLUSIONS: Non-contrast aMRI provided good visualisation of the liver and detection of abnormalities in patients with inadequate US. aMRI should be further explored in a larger, prospective study as an alternative surveillance strategy in patients with inadequate US.
ABSTRACT
Cholangiocarcinoma (CCA) represents a heterogenous set of malignancies arising from the biliary tract. Classification of CCA subdivides tumours into intrahepatic (iCCA) and extrahepatic (eCCA), with eCCA further categorised as perihilar (pCCA) and distal (dCCA) lesions. Tumour subtypes show distinct epidemiological, genetic and clinical characteristics. Global incidence and mortality are rising, with the highest rates seen in Asian populations compared to the West. There has been a divergence in recent mortality trends observed between CCA subtypes, with rising rates of iCCA seen compared with eCCA. There are several drivers for these differing trends, including specific risk factors, misclassification of CCA subtypes and variation in diagnosis and surveillance. Risk factors for CCA can be divided into hepatobiliary, extra-hepatic and environmental, with hepatobiliary diseases conferring the largest risk. Surgery represents the only curative treatment for CCA, but can only be offered to early-stage candidates who are otherwise fit; the majority of patients are therefore treated with chemotherapy and, recently, immunotherapy. Due to late-stage presentation of disease, prognosis is poor, with 5-year survival <20%.
ABSTRACT
INTRODUCTION: The COVID-19 pandemic has caused severe disruption of healthcare services worldwide and interrupted patients' access to essential services. During the first lockdown, many healthcare services were shut to all but emergencies. In this study, we aimed to determine the immediate and long-term indirect impact of COVID-19 health services utilisation on hepatocellular cancer (HCC) outcomes. METHODS: A prospective cohort study was conducted from 1 March 2020 until 30 June 2020, correlating to the first wave of the COVID-19 pandemic. Patients were enrolled from tertiary hospitals in the UK and Germany with dedicated HCC management services. All patients with current or past HCC who were discussed at a multidisciplinary meeting (MDM) were identified. Any delay to treatment (DTT) and the effect on survival at one year were reported. RESULTS: The median time to receipt of therapy following MDM discussion was 49 days. Patients with Barcelona Clinic Liver Cancer (BCLC) stages-A/B disease were more likely to experience DTT. Significant delays across all treatments for HCC were observed, but delay was most marked for those undergoing curative therapies. Even though severe delays were observed in curative HCC treatments, this did not translate into reduced survival in patients. CONCLUSION: Interruption of routine healthcare services because of the COVID-19 pandemic caused severe delays in HCC treatment. However, DTT did not translate to reduced survival. Longer follow is important given the delay in therapy in those receiving curative therapy.
ABSTRACT
Liver sinusoidal endothelial cells (LSEC) form a unique barrier between the liver sinusoids and the underlying parenchyma, and thus play a crucial role in maintaining metabolic and immune homeostasis, as well as actively contributing to disease pathophysiology. Whilst their endocytic and scavenging function is integral for nutrient exchange and clearance of waste products, their capillarisation and dysfunction precedes fibrogenesis. Furthermore, their ability to promote immune tolerance and recruit distinct immunosuppressive leukocyte subsets can allow persistence of chronic viral infections and facilitate tumour development. In this review, we present the immunological and barrier functions of LSEC, along with their role in orchestrating fibrotic processes which precede tumourigenesis. We also summarise the role of LSEC in modulating the tumour microenvironment, and promoting development of a pre-metastatic niche, which can drive formation of secondary liver tumours. Finally, we summarise closely inter-linked disease pathways which collectively perpetuate pathogenesis, highlighting LSEC as novel targets for therapeutic intervention.