Impact of the COVID-19 pandemic on patients with hepatocellular carcinoma in the West of Scotland: a cohort study.

OBJECTIVE: The COVID-19 pandemic had an undoubted impact on the provision of elective and emergency cancer care, including the diagnosis and management of patients with hepatocellular carcinoma (HCC). Our aim was to determine the effects of the COVID-19 pandemic on patients with HCC in the West of Scotland. DESIGN: This was a retrospective audit of a prospectively collated database of patients presented to the West of Scotland Multidisciplinary Team (MDT) between April and October 2020 (during the pandemic), comparing baseline demographics, characteristics of disease at presentation, diagnostic workup, treatment and outcomes with patients from April to October 2019 (pre pandemic). RESULTS: There was a 36.5% reduction in new cases referred to the MDT during the pandemic. Patients presented at a significantly later Barcelona Cancer Liver Clinic stage (24% stage D during the pandemic, 9.5% pre pandemic, p<0.001) and with a significantly higher Child-Pugh Score (46% Child-Pugh B/C during the pandemic vs 27% pre pandemic, p<0.001). We observed a reduction in overall survival (OS) among all patients with a median OS during the pandemic of 6 months versus 17 months pre pandemic (p=0.048). CONCLUSION: The impact of the COVID-19 pandemic is likely to have contributed to a reduction in the presentation of new cases and survival among patients with HCC in the West of Scotland. The reason for this is likely multifactorial, but disruption of standard care is likely to have played a significant role. Resources should be provided to address the backlog and ensure there are robust investigation and management pathways going forward.

Mortality and morbidity of locally acquired hepatitis E in the national Scottish cohort: a multicentre retrospective study.

BACKGROUND: Hepatitis E virus (HEV) is the most common acute viral hepatitis in Scotland. Little is known about the burden of morbidity and mortality, which can be high in chronic liver disease or immunocompromised states. AIMS: To record the morbidity and mortality of HEV in Scotland. METHODS: Demographic, clinical and laboratory data were collected retrospectively from all cases of HEV reported to virology departments across nine NHS health boards, between January 2013 and January 2018. RESULTS: Five hundred and eleven cases were included (Mean age 62, 64% male). 58 (11%) cases had pre-existing cirrhosis and 110 (21%) had diabetes. Three hundred and three patients required admission (59%), totalling 2747 inpatient bed days. Seventeen (3.3%) HEV-related deaths were recorded. Factors that predicted mortality included haematological malignancy (OR 51.56, 95% CI 3.40-782.83, P = 0.005), cirrhosis (OR 41.85, 95% CI 2.85-594.16, P = 0.006), higher serum bilirubin (OR 1.01, 95% CI 1.01-1.02, P = 0.011) and chronic HEV infection (OR 0.02, 95% CI 0.02-0.28, P < 0.001). HEV infection affected 35 transplant patients of 106 total immunosuppressed patients (21%). Of these, 25 patients received Ribavirin therapy with a sustained virological remission of 76%. Thirty-five (6.7%) patients developed acute or acute-on-chronic liver failure with two requiring transplant. Thirty-seven (7.2%) patients reported neurological complications with 10 developing neuralgic amyotrophy, 6 Guillain-Barré and 2 encephalitis. Forty-four (8.6%) patients developed acute kidney injury. CONCLUSION: In Scotland, HEV causes a significant burden of inpatient admissions, organ failure and death. Cirrhosis and haematological malignancy are significant predictors of mortality. Neurological and renal complications occur in a significant minority.

Histological Assessment of Gonads in DSD: Relevance for Clinical Management.

Malignant gonadal germ cell tumors, referred to as germ cell cancers (GCC), occur with increased frequency in individuals who have specific types of differences (disorders) of sex development (DSD). Recent population-based studies have identified new environmental and genetic risk factors that have led to a 'genvironment' hypothesis, which may potentially be helpful in risk assessment in DSD-related GCC. In DSD, the malignancy risk is highly heterogeneous, but recent studies allow now to discriminate between high- and low-risk conditions. Gonadal biopsy is in some cases the best procedure of choice to assess the risk, and with the availability of immunohistochemical biomarkers [OCT3/4 (POU5F1), TSPY, SOX9, FOXL2 and KITLG (SCF)], a reliable classification of GCC and its precursors can be made. The opportunities in the field of virtual diagnostic pathology will be presented, having possibilities for rare diseases in general and DSD specifically. It is expected that the International DSD Registry will stimulate international collaborations, facilitating better diagnostic procedures as well as research.

Diagnostic Accuracy of the Combination of Clinical Symptoms and CT or MR Angiography in Patients With Chronic Gastrointestinal Ischemia.

BACKGROUND: No golden diagnostic standard is available to diagnose chronic gastrointestinal ischemia (CGI). GOALS: We aimed to establish an accurate prediction model for CGI, based on clinical symptoms and radiologic evaluation of the amount of stenosis in the celiac artery (CA) and superior mesenteric artery (SMA) by means of computed tomography-angiography or magnetic resonance (MR)-angiography. STUDY: We prospectively included 436 consecutive patients with clinical suspicion of CGI in a tertiary referral center. Predictors for CGI were obtained by comparing clinical parameters to the diagnosis of CGI. Multivariable logistic regression was used to combine the strongest predictors in a model. A score chart based on the prediction model was provided to calculate the risk of CGI. RESULTS: CGI was present in 171/436 (39%) patients (67 y; range, 54 to 74 y; 27% male). Strongest predictors for CGI were female gender [odds ratio (OR)=1.44; 95% confidence interval (CI), 0.85-2.43], weight loss (OR=1.63, 95% CI, 0.98-2.72), concomitant cardiovascular disease (OR=1.70, 95% CI, 1.04-2.78), duration of symptoms (OR=0.88, 95% CI, 0.79-0.99), and stenosis of CA and SMA (50% to 70% stenosis CA: OR=1.33, 95% CI, 0.56-3.19; >70% stenosis CA: OR=5.79, 95% CI, 3.42-9.81; 50% to 70% stenosis SMA: OR=3.21, 95% CI, 0.81-12.74; >70% stenosis SMA: OR=4.39, 95% CI, 2.30-8.41). A model based on clinical symptoms alone showed limited discriminative ability for diagnosing CGI (c-statistic 0.62). Adding radiologic imaging of the mesenteric arteries improved the discriminative ability (c-statistic 0.79). CONCLUSIONS: Clinical symptoms alone are insufficient to predict the risk of CGI. Radiologic evaluation of the mesenteric arteries is essential. This tool may be useful for clinicians to assess the risk of CGI and to decide whether further diagnostic work-up for CGI is needed.

Tailoring the hydrophobicity of graphene for its use as nanopores for DNA translocation.

Graphene nanopores are potential successors to biological and silicon-based nanopores. For sensing applications, it is however crucial to understand and block the strong nonspecific hydrophobic interactions between DNA and graphene. Here we demonstrate a novel scheme to prevent DNA-graphene interactions, based on a tailored self-assembled monolayer. For bare graphene, we encounter a paradox: whereas contaminated graphene nanopores facilitated DNA translocation well, clean crystalline graphene pores very quickly exhibit clogging of the pore. We attribute this to strong interactions between DNA nucleotides and graphene, yielding sticking and irreversible pore closure. We develop a general strategy to noncovalently tailor the hydrophobic surface of graphene by designing a dedicated self-assembled monolayer of pyrene ethylene glycol, which renders the surface hydrophilic. We demonstrate that this prevents DNA to adsorb on graphene and show that single-stranded DNA can now be detected in graphene nanopores with excellent nanopore durability and reproducibility.