Chromosome 9p deletion in clear cell renal cell carcinoma predicts recurrence and survival following surgery

BACKGROUND: Wider clinical applications of 9p status in clear cell renal cell carcinoma (ccRCC) are limited owing to the lack of validation and consensus for interphase fluorescent in situ hybridisation (I-FISH) scoring technique. The aim of this study was to analytically validate the applicability of I-FISH in assessing 9p deletion in ccRCC and to clinically assess its long-term prognostic impact following surgical excision of ccRCC. METHODS: Tissue microarrays were constructed from 108 renal cell carcinoma (RCC) tumour paraffin blocks. Interphase fluorescent in situ hybridisation analysis was undertaken based on preset criteria by two independent observers to assess interobserver variability. 9p status in ccRCC tumours was determined and correlated to clinicopathological variables, recurrence-free survival and disease-specific survival. RESULTS: There were 80 ccRCCs with valid 9p scoring and a median follow-up of 95 months. Kappa statistic for interobserver variability was 0.71 (good agreement). 9p deletion was detected in 44% of ccRCCs. 9p loss was associated with higher stage, larger tumours, necrosis, microvascular and renal vein invasion, and higher SSIGN (stage, size, grade and necrosis) score. Patients with 9p-deleted ccRCC were at a higher risk of recurrence (P=0.008) and RCC-specific mortality (P=0.001). On multivariate analysis, 9p deletion was an independent predictor of recurrence (hazard ratio 4.323; P=0.021) and RCC-specific mortality (hazard ratio 4.603; P=0.007). The predictive accuracy of SSIGN score improved from 87.7% to 93.1% by integrating 9p status to the model (P=0.001). CONCLUSIONS: Loss of 9p is associated with aggressive ccRCC and worse prognosis in patients following surgery. Our findings independently confirm the findings of previous reports relying on I-FISH to detect 9p (CDKN2A) deletion

Assessment of background levels of autoantibodies as a prognostic marker for severe SARS-CoV-2 infection

This project was funded by The Lung Foundation.Background : Patients with more severe forms of SARS-CoV-2 exhibit activation of immunological cascades. Participants (current or ex-smokers with at least 20 years pack history) in a trial (Early Diagnosis of Lung Cancer, Scotland [ECLS]) of autoantibody detection to predict lung cancer risk had seven autoantibodies measured 5 years before the pandemic. This study compared the response to Covid infection in study participants who tested positive and negative to antibodies to tumour-associated antigens: p53, NY-ESO-1, CAGE, GBU4-5, HuD, MAGE A4 and SOX2. Methods : Autoantibody data from the ECLS study was deterministically linked to the EAVE II database, a national, real-time prospective cohort using Scotland’s health data infrastructure, to describe the epidemiology of SARS-CoV-2 infection, patterns of healthcare use and outcomes. The strength of associations was explored using a network algorithm for exact contingency table significance testing by permutation. Results : There were no significant differences discerned between SARS-CoV-2 test results and EarlyCDT-Lung test results (p = 0.734). An additional analysis of intensive care unit (ICU) admissions detected no significant differences between those who tested positive and negative. Subgroup analyses showed no difference in COVID-19 positivity or death rates amongst those diagnosed with chronic obstructive pulmonary disease (COPD) with positive and negative EarlyCDT results. Conclusions : This hypothesis-generating study demonstrated no clinically valuable or statistically significant associations between EarlyCDT positivity in 2013-15 and the likelihood of SARS-CoV-2 positivity in 2020, ICU admission or death in all participants (current or ex-smokers with at least 20 years pack history) or in those with COPD or lung cancer.Publisher PDFPeer reviewe

A gender-sensitised weight loss and healthy living programme for overweight and obese men delivered by Scottish Premier League football clubs (FFIT): a pragmatic randomised controlled trial.

BACKGROUND: The prevalence of male obesity is increasing but few men take part in weight loss programmes. We assessed the effect of a weight loss and healthy living programme on weight loss in football (soccer) fans. METHODS: We did a two-group, pragmatic, randomised controlled trial of 747 male football fans aged 35-65 years with a body-mass index (BMI) of 28 kg/m(2) or higher from 13 Scottish professional football clubs. Participants were randomly assigned with SAS (version 9·2, block size 2-9) in a 1:1 ratio, stratified by club, to a weight loss programme delivered by community coaching staff in 12 sessions held every week. The intervention group started a weight loss programme within 3 weeks, and the comparison group were put on a 12 month waiting list. All participants received a weight management booklet. Primary outcome was mean difference in weight loss between groups at 12 months, expressed as absolute weight and a percentage of their baseline weight. Primary outcome assessment was masked. Analyses were based on intention to treat. The trial is registered with Current Controlled Trials, number ISRCTN32677491. FINDINGS: 374 men were allocated to the intervention group and 374 to the comparison group. 333 (89%) of the intervention group and 355 (95%) of the comparison group completed 12 month assessments. At 12 months the mean difference in weight loss between groups, adjusted for baseline weight and club, was 4·94 kg (95% CI 3·95-5·94) and percentage weight loss, similarly adjusted, was 4·36% (3·64-5·08), both in favour of the intervention (p<0·0001). Eight serious adverse events were reported, five in the intervention group (lost consciousness due to drugs for pre-existing angina, gallbladder removal, hospital admission with suspected heart attack, ruptured gut, and ruptured Achilles tendon) and three in the comparison group (transient ischaemic attack, and two deaths). Of these, two adverse events were reported as related to participation in the programme (gallbladder removal and ruptured Achilles tendon). INTERPRETATION: The FFIT programme can help a large proportion of men to lose a clinically important amount of weight; it offers one effective strategy to challenge male obesity. FUNDING: Scottish Government and The UK Football Pools funded delivery of the programme through a grant to the Scottish Premier League Trust. The National Institute for Health Research Public Health Research Programme funded the assessment (09/3010/06)

Hidden in plain sight:Using administrative data to conduct a longitudinal cohort study of children exposed to opioids in pregnancy

Objectives: Children of women who use substances are difficult to research at a population-level using traditional research methods due to the complexity of their lives. Resultingly, we have little robust evidence on their outcomes. This study developed an administrative data cohort of children exposed to opioids and explored health outcomes.Methods: Using data from birth records, antenatal records, prescription data, hospital/psychiatric hospital admissions, and drug and alcohol service data, we identified 6,408 children (born 2009-2019) in Scotland who were exposed to opioids through illicit use and/or medication assisted treatment (i.e. methadone/buprenorphine). A control group (n. 19,089) of children not exposed to opioids were matched on age of mother and Scottish Index of Multiple Deprivation. Data were described and linear and logistic regression models were used to examine the relationship between risk factors (such as drug and alcohol use in pregnancy, gestation at booking and at birth), and key early outcomes.Results: Although the majority of women had their substance use recorded in antenatal records, 28.9\% did not, demonstrating the importance of using multiple administrative datasets to form the cohort. Children in the cohort were more likely to experience a range of adverse outcomes including being born early (17\% born prematurely, compared with 6.5\% in control group), having a below normal Apgar score (the scoring system used to assess newborns shortly after birth) (2.9\% in cohort vs. 1.5\% in controls), having significantly lower birthweight, length and head circumference, and more likely to be removed from their mother prior hospital discharge. Differences between the cohorts remained after controlling for other risk factors including alcohol use, and gestation.Conclusion: This feasibility study brought together a cohort of children usually excluded from traditional forms of research. The research demonstrated early differences in outcomes between exposed children and others from similar socio-economic groups. The next stage of this research is exploring health and development outcomes in the preschool period

Indication for percutaneous aortic valve implantation

The incidence of valvular aortic stenosis has increased over the past decades due to improved life expectancy. Surgical aortic valve replacement is currently the only treatment option for severe symptomatic aortic stenosis that has been shown to improve survival. However, up to one third of patients who require lifesaving surgical aortic valve replacement are denied surgery due to high comorbidities resulting in a higher operative mortality rate. In the past such patients could only be treated with medical therapy or percutaneous aortic valvuloplasty, neither of which has been shown to improve mortality. With advances in interventional cardiology, transcatheter methods have been developed for aortic valve replacement with the goal of offering a therapeutic solution for patients who are unfit for surgical therapy. Currently there are two catheter-based treatment systems in clinical application (the Edwards SAPIEN aortic valve and the CoreValve ReValving System), utilizing either a balloon-expandable or a self-expanding stent platform, respectively