Polygenic risk score for ulcerative colitis predicts immune checkpoint inhibitor-mediated colitis.

Immune checkpoint inhibitor-mediated colitis (IMC) is a common adverse event of treatment with immune checkpoint inhibitors (ICI). We hypothesize that genetic susceptibility to Crohn's disease (CD) and ulcerative colitis (UC) predisposes to IMC. In this study, we first develop a polygenic risk scores for CD (PRSCD) and UC (PRSUC) in cancer-free individuals and then test these PRSs on IMC in a cohort of 1316 patients with ICI-treated non-small cell lung cancer and perform a replication in 873 ICI-treated pan-cancer patients. In a meta-analysis, the PRSUC predicts all-grade IMC (ORmeta=1.35 per standard deviation [SD], 95% CI = 1.12-1.64, P = 2×10-03) and severe IMC (ORmeta=1.49 per SD, 95% CI = 1.18-1.88, P = 9×10-04). PRSCD is not associated with IMC. Furthermore, PRSUC predicts severe IMC among patients treated with combination ICIs (ORmeta=2.20 per SD, 95% CI = 1.07-4.53, P = 0.03). Overall, PRSUC can identify patients receiving ICI at risk of developing IMC and may be useful to monitor patients and improve patient outcomes.

Polygenic risk score for ulcerative colitis predicts immune checkpoint inhibitor-mediated colitis.

Immune checkpoint inhibitors (ICIs) are a remarkable advancement in cancer therapeutics; however, a substantial proportion of patients develop severe immune-related adverse events (irAEs). Understanding and predicting irAEs is a key to advancing precision immuno-oncology. Immune checkpoint inhibitor-mediated colitis (IMC) is a significant complication from ICI and can have life-threatening consequences. Based on clinical presentation, IMC mimics inflammatory bowel disease, however the link is poorly understood. We hypothesized that genetic susceptibility to Crohn's disease (CD) and ulcerative colitis (UC) may predispose to IMC. We developed and validated polygenic risk scores for CD (PRSCD) and UC (PRSUC) in cancer-free individuals and assessed the role of each of these PRSs on IMC in a cohort of 1,316 patients with non-small cell lung cancer who received ICIs. Prevalence of all-grade IMC in our cohort was 4% (55 cases), and for severe IMC, 2.5% (32 cases). The PRSUC predicted the development of all-grade IMC (HR=1.34 per standard deviation [SD], 95% CI=1.02-1.76, P=0.04) and severe IMC (HR=1.62 per SD, 95% CI=1.12-2.35, P=0.01). PRSCD was not associated with IMC or severe IMC. The association between PRSUC and IMC (all-grade and severe) was consistent in an independent pan-cancer cohort of patients treated with ICIs. Furthermore, PRSUC predicted severe IMC among patients treated with combination ICIs (OR = 2.20 per SD, 95% CI = 1.07-4.53, P=0.03). This is the first study to demonstrate the potential clinical utility of a PRS for ulcerative colitis in identifying patients receiving ICI at high risk of developing IMC, where risk reduction and close monitoring strategies could help improve overall patient outcomes.

Postoperative ambulation in thoracic surgery patients: standard versus modern ambulation methods.

AIM: A single-subject study of two methods of postoperative ambulation of patients recovering from thoracic surgery. BACKGROUND: During the postoperative setting, patients are often burdened by their condition that reduces their ability to ambulate. This problem is compounded by the addition of devices that make walking more cumbersome. To simplify the process of ambulation during the postoperative period, an intravenous pole/walker (IVPW) was specifically designed to allow all patient devices and attachments to accompany the patient during ambulation, without the need for supplemental caregiver assistance. METHODS: The IVPW method of ambulation was compared with standard method of ambulation (SMA) in a single-subject clinical trial. Thirty-nine consecutive thoracic surgery patients with at least an IV and chest tube were ambulated using alternatively either the IVPW or the SMA. Immediately following the ambulation periods, the patient and patient's health care worker assessed both methods using satisfaction surveys consisting of several questions about the episodes of ambulation and the number of health care workers needed to assist during ambulation. RESULTS: Patient satisfaction was significantly higher in the ability of the IVPW to provide support and assist in ambulation in comparison with the SMA (p < 0·001). Nurses felt the IVPW both facilitated and provided a safer method for ambulation compared with the SMA (p < 0·001). On average, one less employee was required during ambulation with the IVPW (p < 0·001). CONCLUSION: The IVPW provided better support and was perceived as a safer method for ambulation compared with the SMA. The IVPW also required one less person to assist with ambulation. RELEVANCE TO CLINICAL PRACTICE: Facilitation of ambulation in the postoperative setting can impact nursing care and patient satisfaction.