Artificial intelligence for detection of microsatellite instability in colorectal cancer – a multicentric analysis of a pre-screening tool for clinical application

BACKGROUND: Microsatellite instability (MSI)/mismatch repair deficiency (dMMR) is a key genetic feature which should be tested in every patient with colorectal cancer (CRC) according to medical guidelines. Artificial intelligence (AI) methods can detect MSI/dMMR directly in routine pathology slides, but the test performance has not been systematically investigated with predefined test thresholds. METHOD: We trained and validated AI-based MSI/dMMR detectors and evaluated predefined performance metrics using nine patient cohorts of 8343 patients across different countries and ethnicities. RESULTS: Classifiers achieved clinical-grade performance, yielding an area under the receiver operating curve (AUROC) of up to 0.96 without using any manual annotations. Subsequently, we show that the AI system can be applied as a rule-out test: by using cohort-specific thresholds, on average 52.73% of tumors in each surgical cohort [total number of MSI/dMMR = 1020, microsatellite stable (MSS)/ proficient mismatch repair (pMMR) = 7323 patients] could be identified as MSS/pMMR with a fixed sensitivity at 95%. In an additional cohort of N = 1530 (MSI/dMMR = 211, MSS/pMMR = 1319) endoscopy biopsy samples, the system achieved an AUROC of 0.89, and the cohort-specific threshold ruled out 44.12% of tumors with a fixed sensitivity at 95%. As a more robust alternative to cohort-specific thresholds, we showed that with a fixed threshold of 0.25 for all the cohorts, we can rule-out 25.51% in surgical specimens and 6.10% in biopsies. INTERPRETATION: When applied in a clinical setting, this means that the AI system can rule out MSI/dMMR in a quarter (with global thresholds) or half of all CRC patients (with local fine-tuning), thereby reducing cost and turnaround time for molecular profiling

What do Cochrane systematic reviews say about non-surgical interventions for urinary incontinence in women?

ABSTRACT BACKGROUND: Urinary incontinence is a highly prevalent condition that impacts self-esteem and overall quality of life. Many non-surgical treatment options are available, ranging from pharmacological approaches to pelvic exercises. We aimed to summarize the available evidence regarding these non-surgical interventions. DESIGN AND SETTING: Review of systematic reviews, conducted in the Discipline of Evidence-Based Medicine, Escola Paulista de Medicina, Universidade Federal de São Paulo (EPM-UNIFESP). METHODS: A sensitive search was conducted to identify all Cochrane systematic reviews that fulfilled the inclusion criteria. Titles and abstracts were screened by two authors. RESULTS: We included 20 Cochrane systematic reviews: 4 assessing methods of vesical training, 3 evaluating pharmacological interventions, 4 studying pelvic floor muscle training approaches and 9 aimed at other alternatives (such as urethral injections, weighted vaginal cone use, acupuncture, biostimulation and radiofrequency therapy). The reviews found that the evidence regarding the benefits of these diverse interventions ranged in quality from low to high. CONCLUSIONS: This review included 20 Cochrane systematic reviews that provided evidence (of diverse quality) for non-pharmacological interventions for patients with urinary incontinence. Moderate to high quality of evidence was found favoring the use of pelvic floor muscle training among women with urinary incontinence. To establish solid conclusions for all the other comparisons, further studies of good methodological quality are needed.</div