Exploiting the Ref-1-APE1 node in cancer signaling and other diseases: from bench to clinic

Reduction-oxidation factor 1-apurinic/apyrimidinic endonuclease (Ref-1/APE1) is a critical node in tumor cells, both as a redox regulator of transcription factor activation and as part of the DNA damage response. As a redox signaling protein, Ref-1/APE1 enhances the transcriptional activity of STAT3, HIF-1α, nuclear factor kappa B, and other transcription factors to promote growth, migration, and survival in tumor cells as well as inflammation and angiogenesis in the tumor microenvironment. Ref-1/APE1 is activated in a variety of cancers, including prostate, colon, pancreatic, ovarian, lung and leukemias, leading to increased aggressiveness. Transcription factors downstream of Ref-1/APE1 are key contributors to many cancers, and Ref-1/APE1 redox signaling inhibition slows growth and progression in a number of tumor types. Ref-1/APE1 inhibition is also highly effective when paired with other drugs, including standard-of-care therapies and therapies targeting pathways affected by Ref-1/APE1 redox signaling. Additionally, Ref-1/APE1 plays a role in a variety of other indications, such as retinopathy, inflammation, and neuropathy. In this review, we discuss the functional consequences of activation of the Ref-1/APE1 node in cancer and other diseases, as well as potential therapies targeting Ref-1/APE1 and related pathways in relevant diseases. APX3330, a novel oral anticancer agent and the first drug to target Ref-1/APE1 for cancer is entering clinical trials and will be explored in various cancers and other diseases bringing bench discoveries to the clinic

Artificial intelligence-based detection of pneumonia in chest radiographs

Artificial intelligence is gaining increasing relevance in the field of radiology. This study retrospectively evaluates how a commercially available deep learning algorithm can detect pneumonia in chest radiographs (CR) in emergency departments. The chest radiographs of 948 patients with dyspnea between 3 February and 8 May 2020, as well as 15 October and 15 December 2020, were used. A deep learning algorithm was used to identify opacifications associated with pneumonia, and the performance was evaluated by using ROC analysis, sensitivity, specificity, PPV and NPV. Two radiologists assessed all enrolled images for pulmonal infection patterns as the reference standard. If consolidations or opacifications were present, the radiologists classified the pulmonal findings regarding a possible COVID-19 infection because of the ongoing pandemic. The AUROC value of the deep learning algorithm reached 0.923 when detecting pneumonia in chest radiographs with a sensitivity of 95.4%, specificity of 66.0%, PPV of 80.2% and NPV of 90.8%. The detection of COVID-19 pneumonia in CR by radiologists was achieved with a sensitivity of 50.6% and a specificity of 73%. The deep learning algorithm proved to be an excellent tool for detecting pneumonia in chest radiographs. Thus, the assessment of suspicious chest radiographs can be purposefully supported, shortening the turnaround time for reporting relevant findings and aiding early triage

Detection Rate and Clinical Relevance of Ink Tattooing during Balloon-Assisted Enteroscopy

Background and Aims. Balloon-assisted enteroscopy (BAE) is a well-established tool in the diagnosis and therapy of small bowel diseases. Ink tattooing of the small bowel is used to mark pathologic lesions or the depth of small bowel insertion. The purpose of this study was to determine the safety, the detection rate, and the clinical relevance of ink tattooing during BAE. Methods. We performed a retrospective analysis of all 81 patients who received an ink tattooing during BAE between 2010 and 2015. Results. In all patients, ink tattooing was performed with no complications. 26 patients received a capsule endoscopy after BAE. The tattoo could be detected via capsule endoscopy in 19 of these 26 patients. The tattoo of the previous BAE could be detected via opposite BAE in 2 of 11 patients. In 9 patients, ink tattooing influenced the choice of approach for reenteroscopy. In 7 patients, the tattoo was used for intraoperative localization and in 3 patients for intraoperative localization as well as for reenteroscopy. The intraoperative detection rate of the tattoo was 100%. Conclusion. Ink tattooing of the small intestine is a safe endoscopic procedure to mark the depth of scope insertion or a pathologic lesion during balloon-assisted enteroscopy

Cost-effectiveness of artificial intelligence for screening colonoscopy: a modelling study

Background: Artificial intelligence (AI) tools increase detection of precancerous polyps during colonoscopy and might contribute to long-term colorectal cancer prevention. The aim of the study was to investigate the incremental effect of the implementation of AI detection tools in screening colonoscopy on colorectal cancer incidence and mortality, and the cost-effectiveness of such tools. Methods: We conducted Markov model microsimulation of using colonoscopy with and without AI for colorectal cancer screening for individuals at average risk (no personal or family history of colorectal cancer, adenomas, inflammatory bowel disease, or hereditary colorectal cancer syndrome). We ran the microsimulation in a hypothetical cohort of 100 000 individuals in the USA aged 50–100 years. The primary analysis investigated screening colonoscopy with versus without AI every 10 years starting at age 50 years and finishing at age 80 years, with follow-up until age 100 years, assuming 60% screening population uptake. In secondary analyses, we modelled once-in-life screening colonoscopy at age 65 years in adults aged 50–79 years at average risk for colorectal cancer. Post-polypectomy surveillance followed the simplified current guideline. Costs of AI tools and cost for downstream treatment of screening detected disease were estimated with 3% annual discount rates. The main outcome measures included the incremental effect of AI-assisted colonoscopy versus standard (no-AI) colonoscopy on colorectal cancer incidence and mortality, and cost-effectiveness of screening projected for the average risk screening US population. Findings: In the primary analyses, compared with no screening, the relative reduction of colorectal cancer incidence with screening colonoscopy without AI tools was 44·2% and with screening colonoscopy with AI tools was 48·9% (4·8% incremental gain). Compared with no screening, the relative reduction in colorectal cancer mortality with screening colonoscopy with no AI was 48·7% and with screening colonoscopy with AI was 52·3% (3·6% incremental gain). AI detection tools decreased the discounted costs per screened individual from $3400 to$3343 (a saving of $57 per individual). Results were similar in the secondary analyses modelling once-in-life colonoscopy. At the US population level, the implementation of AI detection during screening colonoscopy resulted in yearly additional prevention of 7194 colorectal cancer cases and 2089 related deaths, and a yearly saving of US$290 million. Interpretation: Our findings suggest that implementation of AI detection tools in screening colonoscopy is a cost-saving strategy to further prevent colorectal cancer incidence and mortality. Funding: European Commission and Japan Society of Promotion of Science

Role of gastrointestinal endoscopy in the screening of digestive tract cancers in Europe: European Society of Gastrointestinal Endoscopy (ESGE) Position Statement

In Europe at present, but also in 2040, 1 in 3 cancer-related deaths are expected to be caused by digestive cancers. Endoscopic technologies enable diagnosis, with relatively low invasiveness, of precancerous conditions and early cancers, thereby improving patient survival. Overall, endoscopy capacity must be adjusted to facilitate both effective screening programs and rigorous control of the quality assurance and surveillance systems required