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Pancreatic ductal adenocarcinoma lacks suitable biomarkers for early diagnosis of disease. In gene panels developed for early diagnosis of pancreatic cancer, high AHNAK2 mRNA expression was one possible biomarker. In silico analysis of published human sample datasets (n = 177) and ex vivo analysis of human plasma samples (n = 30 PDAC with matched 30 healthy control) suggested AHNAK2 could be a diagnostic biomarker. At a plasma level of 421.47 ng/ml, AHNAK2 could potentially diagnose PDAC with a specificity and sensitivity of 83.33% and 86.67%. In vitro analysis suggests that in cell lines with diffuse cytoplasmic distribution of AHNAK2, there was colocalization of AHNAK2 with Cortactin in filipodia. This colocalization increased when cells were cultured on substrates such as Fibronectin and Collagen, as well as in hypoxia, and resulted in an augmented invasion of cancer cells. However, in cell lines with a vesicular AHNAK2 staining, such changes were not observed. Our study posits AHNAK2 as a valuable diagnostic biomarker in PDAC, now demanding prospective validation. Determination of mechanisms regulating AHNAK2 subcellular localisation may help explain its biological role.

AHNAK2 is a protein discovered in 2004, with a strong association with oncogenesis in various epithelial cancers. It has a large 616 kDa tripartite structure and is thought to take part in the formation of large multi-protein complexes. High expression is found in clear cell renal carcinoma, pancreatic ductal adenocarcinoma, uveal melanoma, and lung adenocarcinoma, with a relation to poor prognosis. Little work has been done in exploring the function and relation AHNAK2 has with cancer, with early studies showing promising potential as a future biomarker and therapeutic target.

The study aimed to develop a prediction model for differentiating suspected PDAC from benign conditions. We used a prospective cohort of patients with pancreatic disease (n = 762) enrolled at the Barts Pancreas Tissue Bank (2008-2021) and performed a case-control study examining the association of PDAC (n = 340) with predictor variables including demographics, comorbidities, lifestyle factors, presenting symptoms and commonly performed blood tests. Age (over 55), weight loss in hypertensive patients, recent symptoms of jaundice, high serum bilirubin, low serum creatinine, high serum alkaline phosphatase, low red blood cell count and low serum sodium were identified as the most important features. These predictors were then used for training several machine-learning-based risk-prediction models on 75% of the cohort. Models were assessed on the remaining 25%. A logistic regression-based model had the best overall performance in the validation cohort (area-under-the-curve = 0.90; Spiegelhalter’s z = −1·82, p = 0.07). Setting a probability threshold of 0.15 guided by the maximum F2-score of 0.855, 96.8% sensitivity was reached in the full cohort, which could lead to earlier detection of 84.7% of the PDAC patients. The prediction model has the potential to be applied in primary, secondary and emergency care settings for the early distinction of suspected PDAC patients and expedited referral to specialist hepato-pancreatico-biliary services.

1) Context:This audit took place in Glan Clwyd Hospital, a DGH in north Wales. The project involved all patients who were prescribed oxygen in the hospital and was carried out by junior doctors in the respiratory department with senior supervision.2) Issue:The main purpose of the audit was to develop junior doctors as leaders and bring about a meaningful change in a system that was already saturated with audits that were performed as a tick box exercise for curriculum purposes. Incorrect oxygen prescription was an issue which all of the junior doctors identified during their placement and often had profound effects on patient management. We postulated that by performing this audit, we would bring about a very positive effect on the management of patients on oxygen and would result in a major change in practice, all driven by foundation year one doctors.3) Assessment of issue and analysis of its causes:Objectives of the audit were:To check compliance there is with oxygen prescription by doctors according to the ALL Wales Drug Chart, whether the oxygen was prescribed correctly, whether the patient was receiving the correct amount of oxygen as stated on the observations chart and whether the target saturations were met– for this, we divided into groups of two and visited wards, identifying patients on oxygen and going through their drug charts manually.To see how many nurses had received formal oxygen training– this was done as individual interviews of the nursing staff by junior doctors.Whether doctors and nurses were correctly able to interpret oxygen flow rate correctly– this was done in real time by asking doctors and nurses to correctly identify the flow meter reading by the bedside.