Microsatellite instability (MSI) is a molecular marker of deficient DNA mismatch repair (dMMR) that is found in approximately 15% of colorectal cancer (CRC) patients. Testing all CRC patients for MSI/dMMR is recommended as screening for Lynch Syndrome and, more recently, to determine eligibility for immune checkpoint inhibitors in advanced disease. However, universal testing for MSI/dMMR has not been uniformly implemented because of cost and resource limitations. Artificial intelligence has been used to predict MSI/dMMR directly from hematoxylin and eosin (H&E) stained tissue slides. We review the emerging data regarding the utility of machine learning for MSI classification, focusing on CRC. We also provide the clinician with an introduction to image analysis with machine learning and convolutional neural networks. Machine learning can predict MSI/dMMR with high accuracy in high quality, curated datasets. Accuracy can be significantly decreased when applied to cohorts with different ethnic and/or clinical characteristics, or different tissue preparation protocols. Research is ongoing to determine the optimal machine learning methods for predicting MSI, which will need to be compared to current clinical practices, including next-generation sequencing. Predicting response to immunotherapy remains an unmet need.

PURPOSE: Since mandatory fortification of grain products with folic acid in the United States in 1998, folate deficiency has become rare. Some have suggested that serum folate levels should be tested rarely in countries with mandatory folic acid fortification, given low rates of deficiency, high cost per deficiency diagnosis, and low rates of supplementation for those diagnosed as deficient. Given persistent racial, ethnic, and socioeconomic disparities in folate deficiency, these suggestions may not apply to all populations. We examine the rate at which serum testing detected folate deficiency in an urban safety net hospital and the characteristics of folate-deficient patients. METHODS: We reviewed the charts of all inpatients and emergency department patients with low serum folate results at a safety net hospital in Boston in 2018. We collected data concerning demographics, social determinants of health, clinical factors, and whether folate supplementation was prescribed. Finally, we performed a cost analysis. RESULTS: Of 1368 patients tested, 76 (5.5%) met criteria for folate deficiency. Overall, 86.8% of these patients were anemic, and 17.1% had macrocytic anemia; 42% were diagnosed with malnutrition. Common social determinants in folate-deficient patients included birth outside of the United States, homelessness, and alcohol use disorder. Of folate-deficient patients, 88% were newly prescribed folic acid supplementation at discharge. The estimated charge per deficient test was $1278. CONCLUSION: Compared with a nearby institution, serum folate testing at our safety net hospital detected deficiency at a higher rate, incurred a lower charge per deficient test, and was more likely to impact management.

Introduction: Folate deficiency is a known cause of megaloblastic anemia. Serum folate level is therefore a common component of the workup for megaloblastic and other anemias. Following mandatory fortification of grain products with folic acid in the US in 1998, folate deficiency has become relatively rare in both the general population and in hospitalized patients. Some authors have suggested that serum folate levels should be tested rarely if at all in countries with mandatory folic acid fortification given low rates of deficiency, high cost per diagnosis of deficiency, and low rates of supplementation for those found to be deficient. However, given persistent racial, ethnic, and socioeconomic disparities in folate deficiency, these conclusions may not apply to all populations. In this study, we examine the rate at which serum folate testing detected folate deficiency in an urban safety net hospital and the characteristics of patients found to be folate deficient. Methods: All serum folate tests performed on inpatients and emergency department patients in 2018 at a large safety net hospital in Boston were reviewed. Serum folate levels under 4 ng/mL were considered deficient per WHO criteria. We reviewed the charts of all patients found to be folate deficient, collecting demographic data; data concerning social determinants of health; and clinical data such as hematologic lab data, stated reason for testing, and pertinent disease states such as malnutrition and substance use. We also noted whether the medical team acted upon the folate deficiency. Finally, we performed a cost analysis. Results: Out of 1368 patients whose serum folate was tested, 76 patients (5.5%) met criteria for folate deficiency. Of those patients, chart review found that hematologic abnormality was a documented cause of testing for 63%. Overall, 79% of folate deficient patients were anemic, but only 20% had a macrocytic anemia. 42% had a documented diagnosis of malnutrition. Common social determinants in patients found to be folate deficient include birth outside of the US (25%), homelessness (12%), and alcohol use disorder (29%). Of those found to be folate deficient, 93% were either started on folic acid supplementation or had already been prescribed supplementation prior to testing (5%). Given that our institution charges $71 per folate test, the expected charges per deficient test would total $1278. Discussion: While the decreased incidence of folate deficiency after fortification has led many to conclude that serum folate tests have limited utility, our data show that this conclusion may not apply to all populations. The 5.5% rate with which testing detects folate deficiency at our institution, with 46% of 2018 income from Medicaid, was markedly higher than the 0.4% rate reported in a similar study done at nearby hospital that derived 14% of 2018 income from Medicaid (Theisen-Toupal et al. J Hosp. Med. 2013). Comparisons to other studies are limited, as the cutoff for folate deficiency varies significantly between institutions. However, the markedly higher frequency with which folate deficiency was detected at our institution as compared to others suggests that folate testing may still have a role within safety net and many public hospital systems. In addition, serum folate testing may be more cost effective at such hospitals. At our hospital, the charge per deficient folate test was $1278, while previously published data from the nearby hospital described above showed a charge of over $35,000 per result under 4 ng/mL (Theisen-Toupal et al. J Hosp Med 2013). In addition, our results showed that deficient folate results usually prompted change in management. At our hospital, over 90% of folate deficient patients were prescribed a folic acid supplement at discharge, while prior studies reported rates of supplementation in the range of 0-65% (e.g. Ashraf et al. J Gen Intern Med 2008). This may reflect greater cognizance among our providers of nutritional deficiencies associated with social determinants of health common to our patient population. As our results indicated high rates of anemia, malnutrition, immigrant status, and substance use disorders among folate deficient patients, future research may include comparisons between patients found to have normal vs low folate levels. Identifying correlations between folate deficiency and other patient characteristics may help to target testing towards those most likely to benefit. Disclosures No relevant conflicts of interest to declare.