III.

In an increasing proportion of cases, hepatocellular carcinoma (HCC) develops in patients with nonalcoholic fatty liver disease (NAFLD). Mutations in telomerase reverse transcriptase (hTERT) are associated with familial liver diseases. The aim of this study was to examine telomere length and germline hTERT mutations as associated with NAFLD‐HCC. In 40 patients with NAFLD‐HCC, 45 with NAFLD‐cirrhosis and 64 healthy controls, peripheral blood telomere length was evaluated by qRT‐PCR and hTERT coding regions and intron–exon boundaries sequenced. We further analyzed 78 patients affected by primary liver cancer (NAFLD‐PLC, 76 with HCC). Enrichment of rare coding mutations (allelic frequency <0.001) was evaluated by Burden test. Functional consequences were estimated in silico and by over‐expressing protein variants in HEK‐293 cells. We found that telomere length was reduced in individuals with NAFLD‐HCC versus those with cirrhosis (P = 0.048) and healthy controls (P = 0.0006), independently of age and sex. We detected an enrichment of hTERT mutations in NAFLD‐HCC, that was confirmed when we further considered a larger cohort of NAFLD‐PLC, and was more marked in female patients (P = 0.03). No mutations were found in cirrhosis and local controls, and only one in 503 healthy Europeans from the 1000 Genomes Project (allelic frequency = 0.025 vs. <0.001; P = 0.0005). Mutations with predicted functional impact, including the frameshift Glu113Argfs*79 and missense Glu668Asp, cosegregated with liver disease in two families. Three patients carried missense mutations (Ala67Val in homozygosity, Pro193Leu and His296Pro in heterozygosity) in the N‐terminal template‐binding domain (P = 0.037 for specific enrichment). Besides Glu668Asp, the Ala67Val variant resulted in reduced intracellular protein levels. In conclusion, we detected an association between shorter telomeres in peripheral blood and rare germline hTERT mutations and NAFLD‐HCC.

This is the first study to engage directly with palliative care patients and to establish their views on the timing of corneal donation discussions. Patients are willing to discuss donation, and further exploration of patient views in this area should be undertaken.

It is estimated that up to a third of recipients of total knee arthroplasty (TKA) experience chronic pain postoperatively. However, there are no clear indications within the literature that predict which patients are at higher risk of being dissatisfied with their TKA. The Western Ontario and McMaster University Osteoarthritis Index (WOMAC) is one of the most commonly used, patient-reported outcome measures in patients with lower limb osteoarthritis. This review discusses the available evidence surrounding the predictability of the outcome of TKA using the WOMAC score as well as considering further patient factors that have been implicated in the level of improvement post TKA. It may be concluded from the available literature that a combination of knee scores and patient factors would be the most accurate way of predicting those patients most likely to have a good outcome from their TKA. There is some disparity within the literature about which patient factors and reported outcome measure scores lead to a positive postoperative outcome. Patient expectations following the procedure also need to be evaluated, as objective measures on a scoring system do not necessarily equate with the subjective patient experience.

BackgroundNorthern England has been experiencing a persistent rise in the number of primary liver cancers, largely driven by an increasing incidence of hepatocellular carcinoma (HCC) secondary to alcohol-related liver disease and non-alcoholic fatty liver disease. Here we review the effect of the COVID-19 pandemic on primary liver cancer services and patients in our region.ObjectiveTo assess the impact of the COVID-19 pandemic on patients with newly diagnosed liver cancer in our region.DesignWe prospectively audited our service for the first year of the pandemic (March 2020–February 2021), comparing mode of presentation, disease stage, treatments and outcomes to a retrospective observational consecutive cohort immediately prepandemic (March 2019–February 2020).ResultsWe observed a marked decrease in HCC referrals compared with previous years, falling from 190 confirmed new cases to 120 (37%). Symptomatic became the the most common mode of presentation, with fewer tumours detected by surveillance or incidentally (% surveillance/incidental/symptomatic; 34/42/24 prepandemic vs 27/33/40 in the pandemic, p=0.013). HCC tumour size was larger in the pandemic year (60±4.6 mm vs 48±2.6 mm, p=0.017), with a higher incidence of spontaneous tumour haemorrhage. The number of new cases of intrahepatic cholangiocarcinoma (ICC) fell only slightly, with symptomatic presentation typical. Patients received treatment appropriate for their cancer stage, with waiting times shorter for patients with HCC and unchanged for patients with ICC. Survival was associated with stage both before and during the pandemic. 9% acquired COVID-19 infection.ConclusionThe pandemic-associated reduction in referred patients in our region was attributed to the disruption of routine healthcare. For those referred, treatments and survival were appropriate for their stage at presentation. Non-referred or missing patients are expected to present with more advanced disease, with poorer outcomes. While protective measures are necessary during the pandemic, we recommend routine healthcare services continue, with patients encouraged to engage.

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For multifactorial reasons an estimated 20% of patients remain unsatisfied after total knee arthroplasty (TKA).Appropriate tension of the soft tissue envelope encompassing the knee is important in total knee arthroplasty and soft tissue imbalance contributes to several of the foremost reasons for revision TKA, including instability, stiffness and aseptic loosening.There is debate in the literature surrounding the optimum way to achieve balancing of a total knee arthroplasty and there is also a lack of an accepted definition of what a balanced knee replacement is.It may be intuitive to use the native knee as a model for balancing; however, there are many difficulties with translating this into a successful prosthesis.One of the foundations of TKA, as described by Insall, was that although the native knee has more weight transmitted through the medial compartment this was to be avoided in a TKA as it would lead to uneven wear and early failure. There is a focus on achieving symmetrical tension and pressure and subsequent ‘balance’ in TKA, but the evidence from cadaveric studies is that the native knee is not symmetrically balanced.As we are currently trying to design an implant that is not based on its anatomical counterpart, is it possible to create a truly balanced prosthesis or to even to define what that balance is? The authors have reviewed the current evidence surrounding TKA balancing and its relationship with the native knee.Cite this article: EFORT Open Rev 2018;3:614-619. DOI: 10.1302/2058-5241.3.180008.

The literature for and against a link between ALBC and the development of microbiological resistance is reviewed and presented. It is concluded that further research is needed to develop a defined set of indications for the use of ALBC in the management of periprosthetic joint infection. In addition, further research into alternative antimicrobial therapies in this area should be encouraged.