Investigating the poor outcomes of BRAF - mutant advanced colorectal cancer: Analysis from 2530 patients in randomised clinical trials

Background: To improve strategies for the treatment of BRAF-mutant advanced colorectal cancer (aCRC) patients we examined individual data from patients treated with chemotherapy alone in three randomised trials to identify points on the treatment pathway where outcomes differ from BRAF wild-types. Patients and Methods: 2530 aCRC patients were assessed from three randomised trials. End-points were progression free survival (PFS), response rate (RR), disease control rate (DCR), post-progression survival (P-PS) and overall survival (OS). Treatments included first-line oxaliplatin/fluorouracil (OxFU), and second-line irinotecan. Clinicians were unaware of BRAF-status Results 231 patients (9.1%) had BRAF-mutant tumours. BRAF-mutation conferred significantly worse survival independent of associated clinicopathological factors known to be prognostic. Compared with wild-type, BRAF-mutant patients treated with first-line OxFU had similar DCR (59.2% vs 72%; adjusted OR=0.76,p=0.24) and PFS (5.7 vs 6.3 months; adjusted HR=1.14, p=0.26). Following progression on first-line chemotherapy, BRAF-mutant patients had a markedly shorter P-PS (4.2 vs 9.2 months, adjusted HR=1.69,p6 months; OS=24.0 months), however 36.5% progressed rapidly through first-line chemotherapy and thereafter, with OS=4.7 months. Conclusions BRAF-mutant aCRC confers a markedly worse prognosis independent of associated clinicopathological features. Chemotherapy provides meaningful improvements in outcome throughout treatment lines. Post-progression survival is markedly worse and vigilance is required to ensure appropriate delivery of treatment after first-line progression

Multi-drug resistant Escherichia coli in diarrhoeagenic foals: Pulsotyping, phylotyping, serotyping, antibiotic resistance and virulence profiling

Extraintestinal pathogenic E. coli (ExPEC) possess the ability to cause extraintestinal infections such as urinary tract infections, neonatal meningitis and sepsis. While information is readily available describing pathogenic E. coli populations in food-producing animals, studies in companion/sports animals such as horses are limited. In addition, many antimicrobial agents used in the treatment of equine infections are also utilised in human medicine, potentially contributing to the spread of antibiotic resistance determinants among pathogenic strains. The aim of this study was to phenotypically and genotypically characterise the multidrug resistance and virulence associated with 83 equine E. coli isolates recovered from foals with diarrhoeal disease. Serotyping was performed by both PCR and sequencing. Antibiotic resistance was assessed by disc diffusion. Phylogenetic groups, virulence genes, antibiotic resistance genes and integrons were determined by PCR. Thirty-nine (46%) of the isolates were classified as ExPEC and hence considered to be potentially pathogenic to humans and animals. Identified serogroups O1, O19a, O40, O101 and O153 are among previously reported human clinical ExPEC isolates. Over a quarter of the E. coli were assigned to pathogenic phylogroups B2 (6%) and D (23%). Class 1 and class 2 integrons were detected in 85% of E. coli, revealing their potential to transfer MDR to other pathogenic and non-pathogenic bacteria. With 65% of potentially pathogenic isolates harbouring one or more TEM, SHV and CTX-M-2 group β-lactamases, in addition to the high levels of resistance to fluoroquinolones observed, our findings signal the need for increased attention to companion/sport animal reservoirs as public health threats

Alcohol-related emergency department presentations and hospital admissions around the time of minimum unit pricing in Ireland

Background Minimum unit pricing (MUP) was recently introduced in Ireland to reduce alcohol-related harms. The size of the impact of alcohol on hospital emergency departments (EDs) in Ireland is poorly understood due to inconsistent alcohol screening and documentation. Aims We sought to systematically characterise the volume, timing, and nature of alcohol-related presentations and admissions to a busy urban ED in Dublin, Ireland. Method Patients presenting to the ED were assessed by a dedicated clinician during selected time periods before (Nov–Dec 2021) and after (Feb–Apr 2022) the introduction of MUP. A total of 725 interviews were conducted over 168 h in the ED. Findings Alcohol consumption was a factor in 19.4% of ED presentations and in 17.3% of hospital admissions across the entire study period. A reduction in overall alcohol-related ED presentations was noted in the period following MUP, although it is not possible to conclude a direct effect. Conclusion Alcohol-related harm places a significant strain on EDs and hospitals, and the impact of MUP on hospital burden in Ireland merits further evaluation. Effective measures at local and population levels are urgently required to address this burden

Exploring how members of the public access and use health research and information: a scoping review

Background Making high-quality health and care information available to members of the general public is crucial to support populations with self-care and improve health outcomes. While attention has been paid to how the public accesses and uses health information generally (including personal records, commercial product information or reviews on healthcare practitioners and organisations) and how practitioners and policy-makers access health research evidence, no overview exists of the way that the public accesses and uses high quality health and care information. Purpose This scoping review aimed to map research evidence on how the public accesses and uses a specific type of health information, namely health research and information that does not include personal, product and organisational information. Methods Electronic database searches [CINAHL Plus, MEDLINE, PsycInfo, Social Sciences Full Text, Web of Science and SCOPUS] for English language studies of any research design published between 2010–2022 on the public’s access and use of health research or information (as defined above). Data extraction and analysis was informed by the Joanna Briggs Institute protocol for scoping reviews, and reported in accordance with the PRISMA extension for scoping reviews. Results The search identified 4410 records. Following screening of 234 full text studies, 130 studies were included. One-hundred-and-twenty-nine studies reported on the public’s sources of health-research or information; 56 reported the reasons for accessing health research or information and 14 reported on the use of this research and information. The scoping exercise identified a substantial literature on the broader concept of ‘health information’ but a lack of reporting of the general public’s access to and use of health research. It found that ‘traditional’ sources of information are still relevant alongside newer sources; knowledge of barriers to accessing information focused on personal barriers and on independent searching, while less attention had been paid to barriers to access through other people and settings, people’s lived experiences, and the cultural knowledge required. Conclusions The review identified areas where future primary and secondary research would enhance current understanding of how the public accesses and utilises health research or information, and contribute to emerging areas of research

Prevalence of Salmonella serotypes on pig carcasses from high- and low-risk herds slaughtered in three abattoirs

The aim of this study was to compare the prevalence of Salmonella serotypes at two different sites on pig carcasses from herds classified as high-risk or low-risk and to elucidate the relationship between carcass contamination levels and serological status. Caecal samples and carcass surface swabs were cultured for Salmonella from a total of 210 pigs from low risk herds (\u3c 19 % of pigs in herd Salmonella seropositive) and 209 pigs from high risk herds (\u3e 32% of pigs in herd Salmonella seropositive) in three abattoirs

Expression and DNA methylation of TNF, IFNG and FOXP3 in colorectal cancer and their prognostic significance.

BACKGROUND: Colorectal cancer (CRC) progression is associated with suppression of host cell-mediated immunity and local immune escape mechanisms. Our aim was to assess the immune function in terms of expression of TNF, IFNG and FOXP3 in CRC. METHODS: Sixty patients with CRC and 15 matched controls were recruited. TaqMan quantitative PCR and methylation-specific PCR was performed for expression and DNA methylation analysis of TNF, IFNG and FOXP3. Survival analysis was performed over a median follow-up of 48 months. RESULTS: TNF was suppressed in tumour and IFNG was suppressed in peripheral blood mononuclear cells (PBMCs) of patients with CRC. Tumours showed enhanced expression of FOXP3 and was significantly higher when tumour size was >38 mm (median tumour size; P=0.006, Mann-Whitney U-test). Peripheral blood mononuclear cell IFNG was suppressed in recurrent CRC (P=0.01). Methylated TNFpromoter (P=0.003) and TNFexon1 (P=0.001) were associated with significant suppression of TNF in tumours. Methylated FOXP3cpg was associated with significant suppression of FOXP3 in both PBMC (P=0.018) and tumours (P=0.010). Reduced PBMC FOXP3 expression was associated with significantly worse overall survival (HR=8.319, P=0.019). CONCLUSIONS: We have detected changes in the expression of immunomodulatory genes that could act as biomarkers for prognosis and future immunotherapeutic strategies

Prevalence of infection with Salmonella in Irish pig farms

The objectives of this project were to determine the frequency of infection with Salmonella serotypes in Irish pig farms and to identity the point in the production cycle at which infection is acquired. Salmonellae were isolated from pens in 30 of 59 farrow-to-finish farms sampled. Herds classified as low risk were as likely to be positive as high-risk herds. The prevalence of infection was 2.3% in lactating sows, 5.1% in dry sows, 4.6% in gilts, 5.9% in fatteners, 4.8% in second stage weaners and 8.0% in first stage weaners. Prevalence of infection in lactating sows was lower than in other groups sampled (P≥0.005 and was less in second stage than in first stage weaners (P≥0.005). The predominant serotypes isolated were Typhimurium and Derby. Results show that infection was revalent in all production stages. Classification of herds based on serological results of fatteners may not reflect the prevalence of infection in other production stages

Tumour invasiveness, the local and systemic environment and the basis of staging systems in colorectal cancer

background: The present study aimed to examine the relationship between tumour invasiveness (T stage), the local and systemic environment and cancer-specific survival (CSS) of patients with primary operable colorectal cancer. methods: The tumour microenvironment was examined using measures of the inflammatory infiltrate (Klintrup-Makinen (KM) grade and Immunoscore), tumour stroma percentage (TSP) and tumour budding. The systemic inflammatory environment was examined using modified Glasgow Prognostic Score (mGPS) and neutrophil:lymphocyte ratio (NLR). A 5-year CSS was examined. results: A total of 331 patients were included. Increasing T stage was associated with colonic primary, N stage, poor differentiation, margin involvement and venous invasion (P<0.05). T stage was significantly associated with KM grade (P=0.001), Immunoscore (P=0.016), TSP (P=0.006), tumour budding (P<0.001), and elevated mGPS and NLR (both P<0.05). In patients with T3 cancer, N stage stratified survival from 88 to 64%, whereas Immunoscore and budding stratified survival from 100 to 70% and from 91 to 56%, respectively. The Glasgow Microenvironment Score, a score based on KM grade and TSP, stratified survival from 93 to 58%. conclusions: Although associated with increasing T stage, local and systemic tumour environment characteristics, and in particular Immunoscore, budding, TSP and mGPS, are stage-independent determinants of survival and may be utilised in the staging of patients with primary operable colorectal cancer