Clinical outcomes of hepatocellular carcinoma surveillance in Melbourne, Australia.

BACKGROUND: Ultrasound surveillance for hepatocellular carcinoma (HCC) may improve early tumour detection but may additionally result in surveillance-related harm through increased evaluation of non-HCC lesions. The incidence of these outcomes has not been reported outside North America. AIMS: We aimed to report the outcomes of HCC surveillance with respect to both surveillance-related benefits and harms. METHODS: We reviewed all HCC surveillance ultrasounds at a large Victorian tertiary hospital network in 2017 and followed their outcomes until 2021. Surveillance-related benefits were defined as early-stage HCC detection. Surveillance-related harm was defined as contrast imaging, biopsies or surgery performed to evaluate non-HCC liver lesions or false-positive alpha-fetoprotein levels. RESULTS: Five hundred and fifty-three patients were included (mean age 54.5 ± 12.3 years, males 67.5%, cirrhosis 50.3%). The most common liver disease aetiology was hepatitis B (53.9%). Over a median of 4.7 years follow-up, early-stage HCC was detected in 3.3% (5.4% in cirrhotic vs 1.1% in non-cirrhotic patients, P < 0.01). 75% of all HCCs were early-stage. Surveillance-related harm occurred in 12.5% (15.5% in cirrhotic vs 9.5% in non-cirrhotic patients, P < 0.04), although most harm was mild (12.1%). In subgroup analysis, the detection of early-stage HCC ranged between 0% (screened outside of guideline criteria and alcoholic cirrhotic patients) and 7.2% (hepatitis C cirrhosis). Harm occurred between 9% (non-cirrhotic hepatitis B) and 20.8% (thrombocytopenia). CONCLUSION: In our study, HCC surveillance was associated with early tumour detection, although many patients experienced mild surveillance-related harm. Novel surveillance strategies and pathways are required to improve detection in high-risk patients and minimise harm in low-risk patients.

Hepatocellular carcinoma surveillance in Australia: current and future perspectives.

Hepatocellular carcinoma (HCC) is a leading cause of cancer-related death worldwide, and is increasing in incidence in Australia. For most people with cirrhosis and chronic hepatitis B, HCC screening and surveillance is recommended with 6-monthly ultrasound. However, most patients with HCC are still diagnosed outside of surveillance with incurable disease. While HCC surveillance almost certainly reduces cancer-related mortality, the potential harms of surveillance are incompletely understood. Surveillance uptake remains suboptimal in many contexts, and stems from a combination of patient, clinician and system level barriers. Improved case-finding strategies may be required to identify high risk individuals in need of surveillance, as cirrhosis and viral hepatitis are often asymptomatic. HCC prediction models and novel surveillance tools such as biomarker panels, computed tomography and magnetic resonance imaging may have a future role in personalised HCC surveillance. Analyses suggest surveillance may be cost-effective, but Australian data remain limited. A centralised HCC surveillance program may ultimately have a role in delivering improved and more equitable care.

Vedolizumab for induction and maintenance of remission in Crohn's disease.

BACKGROUND: Vedolizumab blocks inflammatory activity within the gastrointestinal tract. Systematic reviews have demonstrated the efficacy of vedolizumab in ulcerative colitis and inflammatory bowel disease in general. This systematic review and meta-analysis summarises the current evidence of vedolizumab in the induction and maintenance of remission in Crohn's disease. OBJECTIVES: To evaluate the benefits and harms of vedolizumab versus placebo for the induction and maintenance of remission in people with Crohn's disease. SEARCH METHODS: We used standard, extensive Cochrane search methods. The latest search date was 30 November 2022. SELECTION CRITERIA: We included randomised controlled trials (RCTs) and quasi-RCTs comparing vedolizumab to placebo for the induction or maintenance of remission in people with Crohn's disease. DATA COLLECTION AND ANALYSIS: We used standard Cochrane methods. For induction studies, the primary outcome was 1. clinical remission, and secondary outcomes were rates of 2. clinical response, 3. adverse events, 4. serious adverse events, 5. surgery, 6. endoscopic remission and 7. endoscopic response. For maintenance studies, the primary outcome was 1. maintenance of clinical remission, and secondary outcomes were rates of 2. adverse events, 3. serious adverse events, 4. surgery, 5. endoscopic remission and 6. endoscopic response. We used GRADE to assess certainty of evidence. MAIN RESULTS: We analysed induction (4 trials, 1126 participants) and maintenance (3 trials, 894 participants) studies representing people across North America, Europe, Asia and Australasia separately. One maintenance trial administered subcutaneous vedolizumab whilst the other studies used the intravenous form. The mean age ranged between 32.6 and 38.6 years. Vedolizumab was superior to placebo for the induction of clinical remission (71 more per 1000 with clinical remission with vedolizumab; risk ratio (RR) 1.61, 95% confidence interval (CI) 1.20 to 2.17; number needed to treat for an additional beneficial outcome (NNTB) 13; 4 studies; high-certainty evidence) and superior to placebo for inducing clinical response (105 more per 1000 with clinical response with vedolizumab; RR 1.43, 95% CI 1.19 to 1.71; NNTB 8; 4 studies; high-certainty evidence). For the induction phase, vedolizumab may be equivalent to placebo for the development of serious adverse events (9 fewer serious adverse events per 1000 with vedolizumab; RR 0.91, 95% CI 0.62 to 1.33; 4 studies; low-certainty evidence) and probably equivalent to placebo for overall adverse events (6 fewer adverse events per 1000 with vedolizumab; RR 1.01, 95% CI 0.93 to 1.11; 4 studies; moderate-certainty evidence). Vedolizumab was superior to placebo for the maintenance of clinical remission (141 more per 1000 with maintenance of clinical remission with vedolizumab; RR 1.52, 95% CI 1.24 to 1.87; NNTB 7; 3 studies; high-certainty evidence). During the maintenance phase, vedolizumab may be equivalent to placebo for the development of serious adverse events (3 fewer serious adverse events per 1000 with vedolizumab; RR 0.98, 95% CI 0.68 to 1.39; 3 studies; low-certainty evidence) and probably equivalent to placebo for the development of overall adverse events (0 difference in adverse events per 1000; RR 1.00, 95% CI 0.94 to 1.07; 3 studies; moderate-certainty evidence). AUTHORS' CONCLUSIONS: High-certainty data across four induction and three maintenance trials demonstrate that vedolizumab is superior to placebo in the induction and maintenance of remission in Crohn's disease. Overall adverse events are probably similar and serious adverse events may be similar between vedolizumab and placebo during both induction and maintenance phases of treatment. Head-to-head research comparing the efficacy and safety of vedolizumab to other biological therapies is required.

Hepatocellular carcinoma surveillance in the telehealth era: A single-centre review.

BACKGROUND: Real-world hepatocellular carcinoma (HCC) surveillance uptake remains suboptimal, despite evidence that surveillance is associated with lower cancer-related mortality in patients with cirrhosis and chronic hepatitis B. We aimed to examine the impact of telehealth consultations on HCC surveillance rates within a specialist liver clinic. METHODS: We conducted a retrospective observational study within an Australian outreach liver clinic within a culturally diverse community, comparing standard consultations before the COVID-19 pandemic to telehealth consultations during the pandemic. The primary outcome was surveillance uptake defined as the percentage of time up-to-date with surveillance (PTUDS) with the 6-month interval following each scan considered up-to-date. RESULTS: Over 18 months of follow-up for each cohort, the median PTUDS was 86.5% in the standard consultation cohort and 85.5% in the telehealth consultation cohort (p = 0.12). HCC diagnoses did not differ between groups and hospitalisation and mortality rates were low. Using multivariate regression, increasing age, the need for an interpreter and being born in South-East Asia independently predicted PTUDS in the standard consultation cohort, whereas being born in Australia or New Zealand was predictive of a lower PTUDS. Current alcohol use and distance from the clinic predicted a lower PTUDS in the telehealth consultation cohort. In both groups, missed clinic attendances were strongly predictive of a lower PTUDS. CONCLUSION: Telehealth hepatology consultations effectively coordinate HCC surveillance and are associated with similar outcomes to standard consultations. Its implementation should be widely considered given its advantages with regards to accessibility for patients.

Prevalence and prognostic significance of vitamin C deficiency in patients with acute upper gastrointestinal bleeding: a prospective cohort study.

BACKGROUND: Vitamin C is an essential dietary nutrient important for collagen synthesis, including within the gastrointestinal tract. AIM: We aimed to document the prevalence of Vitamin C deficiency (VCD) in patients who present with upper gastrointestinal bleeding (UGIB) and its association with clinical outcomes. METHODS: We conducted a prospective cohort study of patients presenting with UGIB. Fasting Vitamin C levels were collected at admission. Primary outcomes were the prevalence of VCD (Vitamin C level <23 µmol/L, severe VCD < 12 µmol/L) and a composite outcome of adverse events, stratified by VCD status. Secondary outcomes were prolonged hospitalisation and the need for ICU admission. RESULTS: A total of 227 patients were included (mean age 64.5 years, males 63.9%). VCD was identified in 74 (32.6%) and severe deficiency in 32 (14.1%) patients. VCD was associated with a higher composite endpoint of AE (45.9% vs 24.8%, p < 0.01), higher in-hospital mortality (9.5% vs 1.3%, p < 0.01), increased prolonged admissions (62.2% versus 47.1%, p = 0.03) and increased rebleeding (17.6% vs 7.8%, p = 0.03), compared with patients with normal Vitamin C levels. Multivariate logistic regression models showed that VCD was independently associated with the composite endpoint of AE. CONCLUSION: VCD is highly prevalent in patients with UGIB and associated with poorer outcomes, including higher mortality, rebleeding and length of stay. Interventional studies are required to determine the impact of early Vitamin C supplementation on clinical outcomes.

Natural history and outcomes of patients with liver cirrhosis complicated by hepatic hydrothorax.

BACKGROUND: Hepatic hydrothorax (HH) is an uncommon and difficult-to-manage complication of cirrhosis with limited treatment options. AIM: To define the clinical outcomes of patients presenting with HH managed with current standards-of-care and to identify factors associated with mortality. METHODS: Cirrhotic patients with HH presenting to 3 tertiary centres from 2010 to 2018 were retrospectively identified. HH was defined as pleural effusion in the absence of cardiopulmonary disease. The primary outcomes were overall and transplant-free survival at 12-mo after the index admission. Cox proportional hazards analysis was used to determine factors associated with the primary outcomes. RESULTS: Overall, 84 patients were included (mean age, 58 years) with a mean model for end-stage liver disease score of 29. Management with diuretics alone achieved long-term resolution of HH in only 12% patients. At least one thoracocentesis was performed in 73.8% patients, transjugular intrahepatic portosystemic shunt insertion in 11.9% patients and 33% patients received liver transplantation within 12-mo of index admission. Overall patient survival and transplant-free survival at 12 mo were 68% and 41% respectively. At multivariable analysis, current smoking [hazard ratio (HR) = 8.65, 95% confidence interval (CI): 3.43-21.9, P < 0.001) and acute kidney injury (AKI) (HR = 2.91, 95%CI: 1.21-6.97, P = 0.017) were associated with a significantly increased risk of mortality. CONCLUSION: Cirrhotic patients with HH are a challenging population with a poor 12-mo survival despite current treatments. Current smoking and episodes of AKI are potential modifiable factors affecting survival. HH is often refractory of diuretic therapy and transplant assessment should be considered in all cases.

Hepatoid adenocarcinoma: A wolf in hepatocellular carcinoma's clothing.

Hepatoid adenocarcinoma (HAC) is a rare malignancy that may mimic hepatocellular carcinoma (HCC) given its hepatoid histologic appearance and production of alpha fetoprotein. Clinical management and prognosis of HAC varies considerably from HCC. We present two cases of metastatic HAC in a cirrhotic liver diagnosed after biopsy and histopathological evaluation. The cases underscore the importance of recognizing the limitations of diagnostic imaging and pursuing a biopsy where there is diagnostic uncertainty.

Spatiotemporal analysis of regional TIA trends.

Background: There has been a decline in the stroke incidence across high income countries but such knowledge exists at Country or State rather than areal unit level such local government area (LGA). In this disease mapping study, we evaluate if there are local hot spots or temporal trends in TIA rate. Such knowledge will be of help in planning healthcare service delivery across regions. Methods: Linked hospital discharge data (Victorian Admitted Episodes Dataset or VAED) was used to collect TIA (defined by ICD-10-AM codes G450-G459) cases from 2001 to 2011. The State of Victoria is the second most populous state in Australia, with a population of 6.7 million and can be divided into 79 administrative units or LGA. The data is anonymized and contains residence of the patient in terms of LGA but not exact location. The date of the TIA event when the patient is admitted to hospital is provided in the dataset. The number of TIAs per year was aggregated for each LGA. Standardized TIA ratios were calculated by dividing actual over expected cases for each LGA per year. We used Integrated Nested Laplace Approximation (INLA) to perform spatial and spatiotemporal regression, adjusting for hypertension, sex and population, age (≥60), and socio-economic status (SES) decile within the LGA. The final model was chosen based on the lowest the Deviance Information Criterion (DIC) and Watanabe-Akaike information criteria (WAIC). Results: Choropleth maps showed a higher standardized TIA ratios in North-West rural region. Compared to the baseline model (DIC 13,159, WAIC 13,261), adding in a spatial random effect significantly improved the model (DIC 6,463, WAIC 6,667). However, adding a temporal component did not lead to a significant improvement (DIC 6,483, WAIC 6,707). Conclusion: Our finding suggests a statically significant spatial component to TIA rate over regional areas but no temporal changes or yearly trends. We propose that such exploratory method should be followed by evaluation of reasons for regional variations and which in turn can identify opportunities in primary prevention of stroke, and stroke care.

Mechanical thrombectomy of symptomatic carotid stenosis with free-floating thrombus in a patient with COVID-19 using transcarotid artery revascularization.

Carotid stenosis with free-floating thrombus is associated with ipsilateral neurologic deficits as a result of cerebrovascular accident or ischemic stroke. Arterial thrombosis and thrombus instability have shown an association with coronavirus disease 2019. Immediate evaluation is essential to assess and prevent thrombus propagation. Traditionally, transfemoral stenting has been performed as minimally invasive intervention. In the present report, we have described the successful use of transcarotid artery revascularization on retrograde flow, aspiration of the thrombus using Penumbra (Penumbra Inc, Alameda, Calif) mechanical thrombectomy, and transcarotid arterial revascularization stenting in a patient with a confirmed case of coronavirus disease 2019.

Mechanical Thrombectomy of Symptomatic Acute Carotid Stent Thrombosis Using Transcarotid Artery Revascularization Neuroprotection Flow Reversal Technique.

Carotid artery stent thrombosis is a relatively rare yet devastating complication of endovascular carotid interventions and manifests as ipsilateral neurological aberrancies such as transient ischemic attack or cerebrovascular accident. Prompt evaluation is necessary, and appropriate imaging is warranted to ascertain the urgency for intervention. Traditionally, anticoagulation with stent explantation and associated thrombectomy is performed. With patients presenting with more high-risk criteria and medical comorbidities, we describe the successful use of transcarotid artery revascularization flow reversal technique with the Penumbra mechanical thrombectomy device to extirpate the thrombus.

Prognostic significance of hepatic encephalopathy in patients with cirrhosis treated with current standards of care.

BACKGROUND: Hepatic encephalopathy (HE) is a reversible neuropsychiatric complication of liver cirrhosis and occurs in up to 50% of cirrhotic patients. Studies examining the prognostic significance of HE are limited despite the high prevalence in cirrhosis. AIM: To define the clinical outcomes of patients after an episode of HE treated with current standards-of-care. METHODS: All patients hospitalised with HE requiring Rifaximin to 3 tertiary centres over 46-mo (2012-2016) were identified via pharmacy dispensing records. Patients with hepatocellular carcinoma and those prescribed Rifaximin prior to admission were excluded. Medical records were reviewed to determine baseline characteristics and survival. The Kaplan-Meier method was used to calculate survival probability. Univariate survival analysis was performed with variables reaching statistical significance included in a multivariate analysis. The primary outcome was 12-mo mortality following commencement of Rifaximin. RESULTS: 188 patients were included. Median age was 57 years (IQR 50-65), 71% were male and median model for end stage liver disease and Child Pugh scores were 25 (IQR 18-31) and 11 (IQR 9-12) respectively. The most common causes of cirrhosis were alcohol (62%), hepatitis C (31%) and non-alcoholic fatty liver disease (20%). A precipitating cause for HE was found in 92% patients with infection (43%), GI bleeding (16%), medication non-compliance (15%) and electrolyte imbalance (14%) the most common. During a mean follow up period of 12 ± 13 mo 107 (57%) patients died and 32 (17%) received orthotopic liver transplantation. The most common causes of death were decompensated chronic liver disease (57%) and sepsis (19%). The probability of survival was 44% and 35% at 12- and 24-mo respectively. At multivariate analysis a model for end stage liver disease > 15 and international normalised ratio reached statistical significance in predicting mortality. CONCLUSION: Despite advances made in the management of HE patients continue to have poor survival. Thus, in all patients presenting with HE the appropriateness of orthotopic liver transplantation should be considered.

Transcatheter Aortic Valve Replacement and Atrial Fibrillation: Impact of Antithrombotic Strategy on Clinical Outcomes.

BACKGROUND: Antithrombotic recommendations following transcatheter aortic valve replacement (TAVR) are largely based on previous trial protocols. The efficacy and risk of anticoagulation has not been systematically assessed. The aim of this study was to determine the efficacy and safety of oral anticoagulation in patients with atrial fibrillation (AF) following TAVR with the Lotus Valve System (Boston Scientific, Marlborough, MA, USA). METHODS: Consecutive patients with severe aortic stenosis who underwent Lotus valve implantation were prospectively recruited (n=164). Atrial fibrillation patients prescribed oral anticoagulation (standard AF therapy) were compared to non-AF patients prescribed aspirin and clopidogrel (standard non-AF therapy). Twenty (20) of 164 patients were excluded, as they were not prescribed standard therapy. The primary endpoint was 6-month incidence of death, myocardial infarction, stroke/transient ischaemic attack (TIA) or major/life-threatening bleeding. Secondary endpoints included each component of the primary endpoint, defined according to VARC-2. RESULTS: Overall, the primary endpoint occurred in 20.8% and 17.7% of the standard AF and standard non-AF therapy groups respectively (p=0.82). There was no statistically significant difference in bleeding (12.5% versus 9.4%, p=0.77) or stroke/TIA (2.1% versus 8.3%, p=0.27) between the standard AF and standard non-AF therapy groups respectively. CONCLUSIONS: This study supports the safety of anticoagulation in AF patients, which did not result in excess risk of bleeding or stroke/TIA compared with dual antiplatelet therapy in non-AF patients.

Clinical Validity, Understandability, and Actionability of Online Cardiovascular Disease Risk Calculators: Systematic Review.

BACKGROUND: Online health information is particularly important for cardiovascular disease (CVD) prevention, where lifestyle changes are recommended until risk becomes high enough to warrant pharmacological intervention. Online information is abundant, but the quality is often poor and many people do not have adequate health literacy to access, understand, and use it effectively. OBJECTIVE: This project aimed to review and evaluate the suitability of online CVD risk calculators for use by low health literate consumers in terms of clinical validity, understandability, and actionability. METHODS: This systematic review of public websites from August to November 2016 used evaluation of clinical validity based on a high-risk patient profile and assessment of understandability and actionability using Patient Education Material Evaluation Tool for Print Materials. RESULTS: A total of 67 unique webpages and 73 unique CVD risk calculators were identified. The same high-risk patient profile produced widely variable CVD risk estimates, ranging from as little as 3% to as high as a 43% risk of a CVD event over the next 10 years. One-quarter (25%) of risk calculators did not specify what model these estimates were based on. The most common clinical model was Framingham (44%), and most calculators (77%) provided a 10-year CVD risk estimate. The calculators scored moderately on understandability (mean score 64%) and poorly on actionability (mean score 19%). The absolute percentage risk was stated in most (but not all) calculators (79%), and only 18% included graphical formats consistent with recommended risk communication guidelines. CONCLUSIONS: There is a plethora of online CVD risk calculators available, but they are not readily understandable and their actionability is poor. Entering the same clinical information produces widely varying results with little explanation. Developers need to address actionability as well as clinical validity and understandability to improve usefulness to consumers with low health literacy.

A comparison of preoperative and intraoperative vein mapping sizes for arteriovenous fistula creation.

BACKGROUND: Duplex ultrasound (DUS) mapping of the veins and arteries of the upper extremity is a well-established practice in arteriovenous fistula creation for long-term hemodialysis access. Previous publications have shown that vein diameters varying from 2 to 3 mm are predictive of success. Regional anesthesia is known to result in vasodilation and thus to increase the diameter of upper extremity veins. This study compares the sizes of veins measured by preoperative DUS mapping with those obtained after regional anesthesia to determine whether intraoperative DUS results in increased vein diameters and thus changes in the operative plan. A second goal was to determine whether such changes resulted in functional access. METHODS: This was a prospective observational study conducted between July 2013 and December 2014. Consecutive patients were preoperatively mapped and then intraoperatively mapped after administration of a regional anesthetic. Comparison of vein mapping sizes and comparison of preoperative plan and operative procedure based on the preoperative and intraoperative DUS mapping, respectively, were analyzed with a repeated-measures linear model. Significance testing was two sided, with a significance level of 5%. RESULTS: Sixty-five patients with end-stage renal disease underwent placement of arteriovenous access with preoperative and intraoperative DUS mapping after regional anesthesia. Comorbidities were representative of the vascular population. After regional anesthesia, intraoperative mid forearm and distal forearm cephalic veins were significantly larger than their respective preoperative measurements. Average increase in diameter of the mid forearm cephalic vein and distal forearm was 0.96 mm (P < .001) and 0.50 mm (P = .04), respectively. There was a significant difference in the number and configuration of arteriovenous accesses (P < .0001). There was more than a twofold significant increase in radial artery-based access procedures concomitant with a significant reduction of brachial-based access procedures and a reduction in graft access procedures. Overall functional access rate was 63%, and patency rates were comparable to those reported in the literature. CONCLUSIONS: The routine use of intraoperative DUS mapping after regional anesthesia is recommended to determine the optimal access site for chronic hemodialysis access. Identifying additional access options not seen with physical examination and preoperative DUS mapping will provide end-stage renal disease patients with more fistula options and hence a longer access life span for a lifelong disease.

Incidence and predictors of permanent pacemaker implantation following treatment with the repositionable Lotus™ transcatheter aortic valve.

OBJECTIVES: To determine the incidence and predictors of permanent pacemaker (PPM) requirement following transcatheter aortic valve replacement (TAVR) with the mechanically expanded LotusTM Valve System (Boston Scientific). BACKGROUND: Pacemaker implantation is the most common complication following TAVR. Predictors of pacing following TAVR with the Lotus valve have not been systematically assessed. METHODS: Consecutive patients with severe aortic stenosis who underwent Lotus valve implantation were prospectively recruited at a single-centre. Patients with a pre-existing PPM were excluded. Baseline ECG, echocardiographic and multiple detector computed tomography as well as procedural telemetry and depth of implantation were independently analyzed in a blinded manner. The primary endpoint was 30-day incidence of pacemaker requirement (PPM implantation or death while pacing-dependent). Multivariate analysis was performed to identify independent predictors of the primary endpoint. RESULTS: A total of 104 consecutive patients underwent TAVR with the Lotus valve with 9/104 (9%) with a pre-existing PPM excluded. New or worsened procedural LBBB occurred in 78%. Thirty-day incidence of the primary pacing endpoint was 28%. The most common indication for PPM implantation was complete heart block (CHB) (69%). Independent predictors of the primary endpoint included pre-existing RBBB (hazard ratio [HR] 2.8, 95% CI 1.1-7.0; P = 0.032) and depth of implantation below the noncoronary cusp (NCC) (HR 2.4, 95% CI 1.0-5.7; P = 0.045). CONCLUSIONS: Almost a third of Lotus valve recipients require pacemaker implantation within 30 days. The presence of pre-existing RBBB and the depth of prosthesis implantation below the NCC were significant pacing predictors. © 2016 Wiley Periodicals, Inc.