The Association of Anemia with Cardiopulmonary Exercise Capacity and Adverse Patient Outcomes in Noncardiac Surgery

Cardiorespiratory impairment and preoperative anemia are associated with postoperative adverse events. Since hemoglobin concentration contributes to oxygen delivery, the association of anemia with outcomes may be due to patient inability to meet postoperative metabolic demands. This thesis examined the association of hemoglobin concentration with two measures of cardiorespiratory reserve, VO2 peak and AT. In patients undergoing major elective surgery, hemoglobin concentration explained 4.9% of the variation in VO2 peak and AT. Each 10 g/L increase in hemoglobin was associated with decreased postoperative complications in a multivariable model adjusted for VO2 peak [aOR 0.86 (95% CI, 0.77-0.96), p=0.007] and AT [aOR 0.86 (95% CI, 0.77-0.97), p=0.01], but not a composite endpoint reflecting end-organ impairment due to decreased systemic oxygen delivery. The magnitude of increased risk for postoperative adverse events associated with anemia is likely small. Interventions mitigating modifiable risk factors, of which anemia is just one, could lead to outcome improvements.M.Sc

Impact of genomic alterations on outcomes in myelofibrosis patients undergoing JAK1/2 inhibitor therapy

In myelofibrosis (MF), driver mutations in JAK2, MPL, or CALR impact survival and progression to blast phase, with the greatest risk conferred by triple-negative status. Subclonal mutations, including mutations in high-molecular risk (HMR) genes, such as ASXL1, EZH2, IDH1/2, and SRSF2 have also been associated with inferior prognosis. However, data evaluating the impact of next-generation sequencing in MF patients treated with JAK1/2 inhibitors are lacking. Using a 54-gene myeloid panel, we performed targeted sequencing on 100 MF patients treated with ruxolitinib (n = 77) or momelotinib (n = 23) and correlated mutational profiles with treatment outcomes. Ninety-nine patients had at least 1 mutation identified, 46 (46%) had 2 mutations, and 34 (34%) patients had >= 3 mutations. Seventy-nine patients carried a mutation in JAK2V617F, 14 patients had mutations in CALR, 6 patients had an MPL mutation, and 2 patients were triple negative. No mutation was significantly associated with spleen or anemia response. A high Dynamic International Prognostic Scoring System score and pretreatment transfusion dependence were associated with a shorter time to treatment failure (TTF), and this association retained significance on multivariable analysis. Patients with ASXL1 (hazard ratio [HR], 1.86; P = .03) and EZH2 mutations (HR, 2.94; P = .009) and an HMR profile (HR, 2.06; P = .01) had shorter TTF. On multivariate analysis, ASXL1 or EZH2 mutations were independently associated with shorter TTF and overall survival. These findings help identify patients unlikely to have a durable response with current JAK1/2 inhibitors and provide a framework for future studies