subclinical relapse (86,87). Higher levels of FC correlate with more endoscopically severe disease, but absolute levels may not correlate with the colonic extent of inflammation. The cutoffs for defining clinical or endoscopic remission and as the optimal therapeutic target have not been studied prospectively and are thus not amenable to the GRADE process. Relevant cutoffs will differ based on whether studies of FC are assessing (i) mucosal healing (by endoscopy or histology) or (ii) clinical relapse and are limited by intrapatient variability (88–90). In separate studies, FC < 60 mg/g and <187 mg/g predicted deep remission (88) and mucosal healing (89), respectively, whereas an FC > 321 mg/g in clinical remission predicted the risk of relapse at 6 and 12 months (91). As with other inflammatory markers, the degree of elevation of FC correlates with burden of inflammation, and values may be normal or borderline in mild disease and may need to be repeated over time. A recent meta-analysis of 25 eligible studies revealed that FC had a pooled sensitivity for endoscopic inflammation in UC of 87.3%, with a specificity of 77.1% and area under the curve of 0.91 (92). This analysis described that the optimum cutoff varied widely by studies, but that the best sensitivity of 90% (87.9–92.9) was achieved at a cutoff level of 50 μg/g, whereas the best specificity of 78.2% (75.7–80.6) was achieved for cutoff levels greater than 100 μg/g (92). In an individual patient, serial FC can be useful as a predictor of response to therapy or relapse. This principle was demonstrated in a phase 3 trial of tofacitinib for moderately to severely active UC, in which serial FC levels were obtained. An FC cutoff value of 150 mg/kg achieved the highest summation of sensitivity and specificity for clinical remission (0.68 and 0.79, respectively; κ coefficient, 0.44) and endoscopic remission (0.79 and 0.75, respectively; κ coefficient, 0.38). More recently, FC levels have been correlated with histologic disease activity as well (93). Further research into optimal cutoffs of FC will guide clinical practice, but the available data support it as an appropriate surrogate to sigmoidoscopy or colonoscopy for assessment and monitoring of mucosal inflammation. MANAGEMENT OF ULCERATIVE COLITIS Therapeutic management in UC should be guided by the specific diagnosis (i.e., Montreal classification), an assessment of disease activity (i.e., mild, moderate, or severe), and disease prognosis. A distinction made in this updated guideline is that treatment selection should be based not only on inflammatory activity but also on disease prognosis. For example, a patient who satisfies the criteria for mildly active disease but who has steroid dependence and a previous hospitalization should be evaluated for treatments typically recommended for patients with moderately to severely active disease because their steroid dependence and previous hospitalization have a significant impact on their disease prognosis. 18. Patients with mildly active UC and a number of prognostic factors associated with an increased risk of hospitalization or surgery should be treated with therapies for moderately to severely active disease (Table 8). Each prognostic factor carries a different weight and must be discussed in a shared decision-making fashion with the patient. For example, age alone is a weaker prognostic factor than severe endoscopic activity. However, young age combined with another factor may represent sufficient criteria to treat according to the moderately to severely